Blood Testing System and Method

ABSTRACT

Some embodiments of a blood coagulation testing system include an analyzer console device and a single-use cartridge component configured to releasably install into the console device. In some embodiments, the blood coagulation testing system can operate as an automated thromboelastometry system that is particularly useful, for example, at a point-of-care site.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is divisional application of Ser. No.14/958,889, “Blood Testing System and Method,” filed Dec. 3, 2015, whichis a continuation in part of U.S. application Ser. No. 14/500,248,“Blood Testing System and Method,” filed on Sep. 29, 2014, the entiredisclosure of which are hereby incorporated by reference, in theirentirety, for all purposes.

TECHNICAL FIELD

This document relates to systems and method for testing characteristicsof a blood sample, such as an automated thromboelastometry system forpoint-of-care whole blood coagulation analysis.

BACKGROUND

Hemostasis is the human body's response to blood vessel injury andbleeding. Hemostasis involves a coordinated effort between platelets andnumerous blood clotting proteins (or clotting factors), resulting in theformation of a blood clot and the subsequent stoppage of bleeding.

Various methods have been introduced to assess the potential of blood toform an adequate clot and to determine the blood clot's stability.Common laboratory tests such as thrombocyte counts or the determinationof fibrin concentration provide information on whether the testedcomponent is available in sufficient amount, but some of those testsmight not answer the question of whether the tested component worksproperly under physiological conditions. Other laboratory tests work onblood plasma, which may impose additional preparation steps andadditional time beyond what is preferred, for example, in thepoint-of-care context (e.g., in a surgical theater during a surgicaloperation).

Another group of tests to assess the potential of blood to form anadequate clot is known as “viscoelastic methods.” In at least someviscoelastic methods, the blood clot firmness (or other parametersdependent thereon) is determined over a period of time, for example,from the formation of the first fibrin fibers until the dissolution ofthe blood clot by fibrinolysis. Blood clot firmness is a functionalparameter which contributes to hemostasis in vivo, as a clot must resistblood pressure and shear stress at the site of vascular injury orincision. In many cases, clot firmness may result from multipleinterlinked processes including coagulation activation, thrombinformation, fibrin formation and polymerization, platelet activation, andfibrin-platelet interaction.

To isolate and test particular functions of thrombocytes, fibrinogen,and other factors in a blood sample, reagent compounds can be mixed withthe blood sample to activate or inhibit certain components in the bloodsample. In some commercially available point-of-care blood testingsystems, liquid reagents are injected into a disposable plastic cupcontaining a blood sample, and the cup is then engaged by the controlconsole of the blood testing system to evaluate characteristics of thecoagulation/clotting of the blood sample. As part of the test process,the system requires manual intervention by the operator for each of theassays, for example, when pipettes are used by an operator for thedispensing and measuring of the reagents, blood, and mixed samples.

SUMMARY

Some embodiments of a system for testing characteristics of a bloodsample (which, as used herein, should be understood to include blood orderivatives of blood such as plasma) can include a cartridge configuredto mate with a control console and receive a blood sample for apoint-of-care whole blood coagulation analysis. In particularcircumstances, the cartridge is configured to interact with the controlconsole so as to perform a number of automated transport and testingoperations on portions of the blood sample so as to provide reliable andprompt results indicative of a patient's blood characteristics at thepoint-of-care (e.g., while the patient is in a surgical room undergoingsurgery). For example, the system can serve as an automatedthromboelastometry system for providing detailed and prompt results ofblood coagulation characteristics in response to receiving a cartridge(and blood sample at the cartridge) and an indication from an operatorto begin the automated testing process.

In some embodiments, the thromboelastometry system includes a reusableanalyzer console and one or more single-use cartridge componentsconfigured to mate with the console. In one example, to operate thethromboelastometry system, a user inserts the cartridge into theanalyzer console and, when prompted by the analyzer console, inserts ablood collection tube (containing a whole blood sample) into a receiverportion of the cartridge. The user is then prompted a user interface ofthe analyzer console to initiate a number of automated blood transferand testing operations. Thereafter, the analyzer console automaticallyperforms (without requiring further user interaction with the cartridgeor the blood sample) the testing and displays the results on a graphicaldisplay using qualitative graphical representations and quantitativeparameters. In this particular example, no manual pipetting, mixing, orhandling of reagents by the user is needed. In some embodiments, four ormore assays are automatically performed on the blood sample using asingle cartridge device. Such assays provide information on the wholekinetics of hemostasis, such as clotting time, clot formation, clotstability, and lysis; moreover, such information can be promptly outputfrom a user interface of the system to provide reliable and promptresults indicative of a patient's blood characteristics at thepoint-of-care (e.g., while the patient is in a surgical room undergoingsurgery).

Particular embodiments described herein include a cartridge for use witha blood testing console. The cartridge may include a blood samplereceiver configured to receive a blood sample to be tested. Thecartridge may also include one or more blood processing and testingpaths. Each blood processing and testing path can receive a portion ofthe blood sample and may include a blood sample volume measurementchamber, a mixing chamber, and a viscoelastic blood testing chamber. Theblood sample volume measurement chamber may be in fluid communicationwith the blood sample receiver, and the blood sample volume measurementchamber may a selected internal volume to contain a predetermined volumeof blood sample from the blood sample container. The mixing chamber maybe in fluid communication with the blood sample volume measurementchamber and with a reagent, and the mixing chamber may be configured toreceive blood sample from the blood sample volume measurement chamberand mix the received blood with the reagent. The viscoelastic bloodtesting chamber may be configured to receive mixed blood and reagentfrom the mixing chamber for a viscoelastic test to be performed on themixed blood and reagent while the mixed blood and reagent resides in thetesting chamber.

In some embodiments described herein, a cartridge device may include ablood sample receiver, and a plurality of blood sample pathways inselective fluid communication with the blood sample receiver. Each bloodsample pathway may include: a blood measurement chamber to receive apredetermined amount of a blood sample via the blood sample receiver, areagent mixing chamber for receiving and mixing the predetermined amountof the blood sample with one or more reagents, and a blood coagulationblood testing chamber for receiving from the reagent mixing chamber theblood sample with one or more reagents mixed therewith. Optionally, theblood coagulation blood testing chamber may have a movable probe thereinfor measuring blood coagulation characteristics.

Various embodiments described herein include a cartridge device for ameasuring system for measuring viscoelastic characteristics of a bloodsample. The cartridge may include a blood sample receiver; and at leastone blood sample pathway in selective fluid communication with the bloodsample receiver. The blood sample pathway may include: a bloodmeasurement chamber configured to be filled with a predetermined amountof a blood sample via the blood sample receiver, a reagent mixingchamber for receiving the predetermined amount of the blood sample fromthe blood measurement chamber and for and mixing the predeterminedamount of the blood sample with one or more reagents, and a bloodcoagulation blood testing chamber for receiving from the reagent mixingchamber the blood sample with one or more reagents mixed therewith, andan overflow chamber in fluid communication with the blood sample pathwayso as to collect excess blood from the blood measurement chamber beyondthe predetermined amount the blood sample. Optionally, the bloodcoagulation blood testing chamber may have a movable probe therein formeasuring blood coagulation characteristics.

Other embodiments described herein include a measuring system formeasuring viscoelastic characteristics of a blood sample. The system mayinclude a control unit housing viscoelastic measurement components. Thecontrol unit may define an exterior port. The system may also include atleast one disposable cartridge comprising a blood sample inputaccessible along an exterior of the cartridge and a plurality of bloodtesting chambers positioned along an interior of the cartridge.Optionally, the control unit is configured to releasably mate with thedisposable cartridge when inserted into the exterior port such that theblood sample input of the cartridge remains external to the control unitwhile the plurality of blood testing chambers are positioned within thecontrol unit.

Some embodiments described herein include a method of using a system formeasuring viscoelastic characteristics of a blood sample. The method mayinclude inserting a disposable cartridge into a blood testing controlconsole such that a blood sample input remains externally exposed. Themethod may also include attaching a blood sample reservoir to the bloodsample input. The method may further include providing user input via auser interface of the blood testing control console so as to initiate anautomated transport of blood in the blood sample reservoir to aplurality of blood testing chambers within the cartridge for measuringviscoelastic characteristics of the blood in each of the blood testingchambers.

In particular embodiments described herein, a cartridge device for ameasuring system for measuring viscoelastic characteristics of a bloodsample may include a blood sample receiver structure defining a cavityconfigured to releasably mate with a blood sample reservoir container.The cartridge device may also include a plurality of blood testingchambers spaced apart from the blood sample receiver structure and eachhaving a movable probe therein for measuring blood coagulationcharacteristics. All of the blood testing chambers may be in selectivefluid communication the blood sample receiver structure.

In some embodiments described herein, a cartridge device for a measuringsystem for measuring viscoelastic characteristics of a blood sample mayinclude a plurality of blood testing chambers for measuring bloodcoagulation characteristics. Each of the blood testing chambers may beexposed to atmosphere and may have a sample input port positioned alonga sidewall of the blood testing chamber. Optionally, each of the bloodtesting chambers is in fluid communication with an output port of arespective reagent mixing chamber that is defined in cartridge device ata height below the sample input port of the blood testing chamber.

In various embodiments described herein, a cartridge device for ameasuring system for measuring viscoelastic characteristics of a bloodsample may include a plurality of reagent mixing chambers for receivingand mixing a predetermined amount of a blood sample with one or morereagent beads. The cartridge device may also include a plurality ofretaining elements extending into the reagent mixing chamber so as tomaintain a predetermined vertical position of each of the reagent mixingbeads within the mixing chamber. The retaining elements of at least oneof the reagent mixing chambers may engage multiple reagent mixing beadsto maintain the multiple reagent mixing beads spaced apart from oneanother.

In particular embodiments described herein, a cartridge device for ameasuring system for measuring viscoelastic characteristics of a bloodsample may include a plurality of reagent mixing chambers for receivingand mixing a predetermined amount of a blood sample with one or morereagent beads. The cartridge device may also include a movable mixingelement retained with the reagent mixing chamber. The movable mixingelement may comprise a material that is inert relative to the bloodsample. The cartridge device may further include a plurality ofretaining elements extending into the reagent mixing chamber so as tomaintain the reagent mixing beads in positions that are spaced apartfrom the movable mixing element.

Some embodiments described herein may include a method for measuringcoagulation characteristics of a blood sample. The method may includedetecting a blood testing cartridge being inserted into a receiverportion of a blood testing control unit. The method may also includeprompting a user for input via a user interface of the blood testingcontrol unit to initiate automated transport of blood in the bloodsample reservoir to one or more blood testing chambers within thecartridge for measuring viscoelastic characteristics of the blood ineach of the blood testing chambers. The method may further includeautomatically transporting to each of the one or more blood testingchambers within the cartridge a predetermined amount of a blood samplefrom a blood sample receiver of the blood testing cartridge. Optionally,the method may also include moving a probe in each respective bloodtesting chamber of the cartridge for measuring blood coagulationcharacteristics. The method may further include displaying via the userinterface measurement results of the blood coagulation characteristics.

Other embodiments described herein include a control console formeasuring coagulation characteristics of a blood sample. The controlconsole may include a control unit housing that houses at least oneinterface element configured to releasably receive a disposablecartridge (which, optionally, may have multiple blood testing chamberstherein, and multiple measurement components configured to measurecoagulation characteristics of the blood sample within the multipleblood testing chambers of the disposable cartridge). The control consolemay also include one or more heating elements positioned proximate tothe interface element and configured to heat the cartridge to apredetermined, test-related temperature (e.g., 37 degrees C. in someembodiments). The control console may further include one or moretemperature sensors positioned proximate to the interface element. Thecontrol unit may be configured to transport blood to the multiple bloodtesting chambers of the disposable cartridge after the temperaturesensors indicate the multiple blood testing chambers of the disposablecartridge have reached a predefined temperature.

Some or all of the embodiments described herein may provide one or moreof the following advantages. First, some embodiments of thethromboelastometry system are configured to be automated so that userinteractions with the system are minimized. As a result, humanresources—especially in a point-of-care context like a surgicaltheater—can be utilized with greater efficiency. The reduction of userinteractions can also reduce the chances for manual operator errors,such as measuring inaccuracies, reagent mixing errors, and the like.Accordingly, more accurate thromboelastometry results may be attained insome circumstances.

Second, in some embodiments, the cartridge component includes multiplefluid channels that are each individually controllable so that multipledifferent assays can be performed from a single supply of a bloodsample. For example, each fluid channel includes a dedicated valve and adedicated vent that are controllable by the analyzer console so that theblood flow and testing of each fluid channel is individuallycontrollable. This feature enables the thromboelastometry system toautomatically perform sophisticated assay processes.

Third, in some embodiments, the analyzer console can be configured toperform a number of quality-control operations/confirmations so as toensure the blood test results are not compromised. For example, theanalyzer console can be configured to verify the blood testing cartridgeis heated to a target temperature (e.g., about 37° C.) prior to theblood sample being distributed to testing chambers of the cartridge.Because temperature of the blood sample can affect the coagulationcharacteristics in some circumstances, the accuracy of thethromboelastometry results may be enhanced as a result of suchtemperature-control operations/confirmations.

Forth, in particular embodiments of the cartridge device, the geometryof the blood flow paths through the fluid channels of the cartridge areconfigured to reduce the potential for disturbing the blood (e.g.,causing bubble formation, etc.), and/or damaging the blood, in a mannerthat may negatively impact the accuracy of the blood test results.

Fifth, in some embodiments, the blood testing cartridge (and,optionally, the blood collection reservoir) can be equipped with one ormore computer-readable components so as to promptly transfer relevantinformation of the analyzer console for each blood sample testing cycle.For example, each cartridge can be labeled with a barcode, near-fieldcommunication tag, and RFID tag, or the like that includes informationsuch as, but not limited to, the types of assays to be performed by thecartridge, the type of reagents container within the cartridge,manufacturer information, an expiration date, or the like. In suchembodiments, the analyzer console can include a barcode reader (or areader for a near-field communication tag, a RFID tag, or the like) thatscans the barcode upon insertion of the cartridge into the analyzerconsole. The analyzer console automatically performs appropriate actionsin response to the data read from the barcode. In another example, eachblood collection reservoir that is to be used with a correspondingcartridge can be labeled with a barcode, near-field communication tag,and RFID tag, or the like that includes information such as, but notlimited to, patient information, clinician information, calibrationinformation, or the like (e.g., which is readable by a correspondingreader device of the analyzer console).

Sixth, each fluid pathway of the cartridge can include a mixing chamberwith one or more reagents and a mixing element located therein. In someembodiments, the reagents comprise dissolvable reagent beads. The mixingchambers of the cartridge can be configured to separate the one or morereagent beads from each other and to inhibit the mixing element fromdirect contact with the reagent beads. Further advantages associatedwith the thromboelastometry systems provided herein are also envisioned,as will be evident from the following disclosure.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIGS. 1A, 1B, 2, and 3 are perspective illustrations depicting thecomponents and use of an example thromboelastometry system, inaccordance with some embodiments.

FIG. 4 is a perspective view of the example cartridge component of thethromboelastometry system of FIGS. 1A, 1B, 2, and 3.

FIG. 5 is an exploded view of the cartridge component of FIG. 4.

FIG. 6 is a right side partial cutaway view of the cartridge componentof FIG. 4.

FIG. 7 is a left side view of the cartridge component of FIG. 4.

FIG. 8A-8H are a series of schematic diagrams depicting operations ofthe thromboelastometry system of FIGS. 1A, 1B, 2, and 3, in accordancewith some embodiments.

FIG. 9 is a schematic diagram of another example thromboelastometrysystem, in accordance with some embodiments.

FIG. 10A is a top view of the cartridge component of FIG. 4.

FIG. 10B is a partial cross-sectional view of the cartridge component ofFIG. 10A.

FIG. 10C is a schematic diagram depicting the partial cross-sectionalview of the cartridge component of FIG. 10B in conjunction withassociated components of an analyzer console of the thromboelastometrysystem of FIGS. 1A, 1B, 2, and 3.

FIG. 11 is an exploded perspective view of a thromboelastometry analyzerconsole of the thromboelastometry system of FIGS. 1A, 1B, 2, and 3.

FIG. 12 is a block diagram that schematically depicts subsystems of thethromboelastometry analyzer console of the thromboelastometry system ofFIGS. 1A, 1B, 2, and 3.

FIG. 13 is a flowchart of a method of using a thromboelastometry system,in accordance with some embodiments.

FIGS. 14A and 14B are a flowchart of a method for controlling athromboelastometry system, in accordance with some embodiments.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

Referring to FIGS. 1A-3, some embodiments of a blood testing system 100include an analyzer console 140 and one or more cartridges 120configured to releasably mate with analyzer console 140. In thisembodiment, the blood testing system 100 is a thromboelastometry systemthat is configured to determine a number of blood coagulationcharacteristics of a blood sample input into the cartridge 120. Forexample, the cartridge 120 can be configured as a single-use cartridgethat includes a blood sample receiver 122 for mating with a blood samplereservoir 10 (e.g., a vacutainer sample tube supplied by Becton,Dickinson & Company of Franklin Lakes, N.J., or another blood reservoirstructure). In some cases, an adapter may be used to couple other typesof blood sample reservoirs 10 with the cartridge 120 (e.g., tubing maybe used through which blood can be injected into the cartridge 120, andthe like). The thromboelastometry system 10 can be used as a whole bloodcoagulation analysis system that is particularly advantageous at apoint-of-care site (e.g., in a surgical theater while a patient isundergoing or preparing for surgery, or the like). Additionally,thromboelastometry system 100 can be used as a whole blood coagulationanalysis system in a laboratory setting.

The analyzer console 140 includes a user interface 142 (with touchscreendisplay in this embodiment) and a main chassis 144. The user interfacedisplay 142 can be configured to output one or more graphical results143 from the blood testing assays performed via the cartridge 120 andconsole 140 (e.g., one or more plots, such as those sometimes refer toas a TEMogram, numeric data or measurements, or a combination thereof).In some embodiments, the user interface display 142 is rigidly attachedto the analyzer console 140. In particular embodiments, the userinterface display 142 is pivotable and/or is otherwise positionallyadjustable in relation to the main chassis 144. A main power switch 148can be located at a convenient but protected location on the mainchassis 144.

In the depicted embodiment, the touchscreen display 142 is configured toreceive user input and to display output information to the user. Forexample, the user can enter information to the thromboelastometry system100 by making selections of various soft-buttons that may be displayedon the touchscreen display 142 at times during the beginning, middle,and end of the testing process. In some embodiments, other selectionssuch as, but not limited to, soft keyboard entries can be provided viatouchscreen display 142. In some embodiments, data entry can beperformed additionally or alternatively by voice entry. In otherembodiments, the user interface may include other peripheral devices canbe included (e.g., a mouse, a keyboard, an additional display device,and the like) as part of the thromboelastometry system 100. In someembodiments, a computer data network (e.g., intranet, internet, LAN,etc.) may be used to allow for remote devices to receive and/or inputinformation from the system 100. For example, in some embodiments one ormore remote displays can be utilized via network connections. In thedepicted embodiment, the thromboelastometry system 100 also includes anexternal barcode reader 146. The external barcode reader 146 canfacilitate convenient one-dimensional or two-dimensional barcode entryof data such as, but not limited to, blood sample data, useridentification, patient identification, normal values, and the like.Alternatively or additionally, the thromboelastometry system 100 can beequipped with a reader configured to read near-field communication tags,RFID tags, or the like.

In the depicted embodiment, the main chassis 144 houses various internalsub-systems (as described further below), includes various electronicconnection receptacles (not shown), and includes a cartridge port 150.The various electronic connection receptacles can include network anddevice connectors such as, but not limited to, one or more USB ports,Ethernet ports (e.g., RJ45), VGA connectors, Sub-D9 connectors (RS232),and the like. Such connection receptacles can be located on the rear ofthe main chassis 144, or at other convenient locations on the mainchassis 144. For example, in some embodiments one or more USB ports maybe located on or near the front of the main chassis 144. A USB port, solocated, may provide user convenience for recording data onto a memorystick, for example. In some embodiments, the thromboelastometry system100 is configured to operate using wireless communication modalitiessuch as, but not limited to, Wi-Fi, Bluetooth, NFC, RF, IR, and thelike.

Still referring to FIGS. 1A-3, the cartridge port 150 can be located ata readily accessible location on the main chassis 144. In the depictedembodiment, the cartridge port 150 is located on the front of the mainchassis 144 so that it is conveniently accessible by a user in apoint-of-care site. The cartridge port 150 defines an opening andinternal space that is shaped complementarily to the outer dimensions ofthe single-use cartridge 120. To insert the single-use cartridge 120into the cartridge port 150, the user can grasp the end of the cartridge120 that includes the blood sample receiver 122 and slidingly insert theopposite end (leading end) into the cartridge port 150. The slidinginsertion can continue until a hard-stop is reached that defines thefully inserted position. In the fully inserted position, a trailing endportion (including the blood sample receiver 122 in this embodiment) ofthe single-use cartridge 120 remains exterior to the main chassis 144.The portion of the cartridge 120 that is received into the cartridgeport 150 can include outer surface features (such as a tapered angle arear end portion shown in FIG. 1B) that mate with at least one internalinterface element inside the console 140 to ensure correct positioningof the cartridge 120. As such, at least the blood sample receiver 122remains exterior to the main chassis 144 throughout the duration of theblood sample testing. In this configuration, the blood sample receiver122 serves as a blood sample well that is accessible so that the bloodsample reservoir 10 can be inserted into the receiver 122 while thesingle-use cartridge 120 is mated with the console 140 in the fullyinserted position. In some embodiments, the cartridge port 150 and themain chassis 144 are configured so that the exposed portion of thecartridge 120 is protected from inadvertent contact. As describedfurther below, an internal sensor (e.g., a microswitch, an opticalsensor, etc.) can detect when the single-use cartridge 120 has beenfully inserted into the main chassis 144.

When the analyzer console 140 has detected that the cartridge 120 hasbeen fully inserted, in some embodiments the analyzer console 140initiates one or more of the following actions. An internal cartridgeclamping mechanism that includes positioning pins can be activated toaccurately position and releasably retain the single-use cartridge 120in the fully inserted position. One or more cartridge heating elementscan be nalactivated to warm the cartridge 120. The temperature of thecartridge 120 can be monitored. A barcode on the leading end of thecartridge 120 can be read and the barcode data can be stored in memoryof the analyzer console 140. One or more blood detection sensors caninspect the cartridge 120 for the presence of blood (which should not bepresent at this time). The rotational thromboelastometry measuringsub-system can be engaged with the cartridge 120 and, optionally,rotation of the rotary thromboelastometry measuring sub-system can begin(without the presence of blood). The cartridge 120 can be leak testedusing vacuum or air pressure delivered by the analyzer console 140. Forexample, a pressure/vacuum decay test can be performed. In someembodiments, other actions can be additionally or alternativelyactivated when the analyzer console 140 has detected that the cartridge120 has been fully inserted. After the completion of such actions, insome embodiments an indication of the results of the actions may bedisplayed on the touchscreen display 142 (e.g., pass or fail). If theanalyzer console 140 determines that the actions were completedsuccessfully, a prompt can be provided on the touchscreen display 142that informs the user that the thromboelastometry system 100 is ready toreceive the blood sample reservoir 10.

Briefly, in some embodiments a user can operate the depictedthromboelastometry system 100 embodiment as follows. First, the user caninsert the single-use cartridge 120 into the cartridge port 150 so thatthe cartridge 120 is placed into the fully inserted position. Completionof that step will automatically initiate a series of operations by thethromboelastometry system 100 as described below. Upon successfulcompletion of such operations, a notification that the blood collectiontube 10 can be inserted into the sample well 122 will be displayed onthe touchscreen display 142. After the user has mated the bloodcollection tube 10 into the sample well 122, the user initiates testingby pressing a “start” button (or the like) on the touchscreen display142. At least the blood measuring, reagent mixing, andthromboelastometry testing is performed automatically by the system 100thereafter (e.g., without requiring manual intervention from the user inthis embodiment). When the testing is completed, the results aredisplayed on the touchscreen display 142 in the form of qualitativegraphical representations and quantitative parameters (e.g., as depictedin FIG. 1A). Also, when the testing is completed, the cartridge 120 canbe removed from the console 140 and discarded (e.g., the cartridge 120in such embodiments is not reusable in that the reagent beads (describedbelow) are no longer present in the cartridge and the measurementchambers contain the clotted blood sample portions).

Alternately, in some embodiments the blood collection tube 10 can beinserted into the sample well 122 of the cartridge 120 prior toinsertion of the cartridge 120 into the cartridge port 150. In suchcircumstances, the blood from the collection tube 10 may not advance tothe measurement chambers (described below) of the blood cartridge 120until after the console 140 acts upon the cartridge 120 (again, asdescribed below). With the blood collection tube 10 being pre-coupledwith the cartridge 120, the combination of the blood collection tube 10and the cartridge 120 can then be inserted into the cartridge port 150.

Referring now to FIGS. 4 and 5, the depicted embodiment of thesingle-use cartridge 120 includes a main body 124, a right cover 126, aleft cover 128, and five pins 138 a, 138 b, 138 c, 138 d, and 138 e. Theright cover 126 is affixed to right side of the main body 124, and theleft cover 128 is affixed to the left side of the main body 124. Assuch, the right and left covers 126 and 128 enclose cavities and flowchannels of the main body 124 to define blood flow paths as describedfurther below. The aforementioned sample well 122 is part of the mainbody 124. However, other constructions of the single use cartridge 120are also envisioned.

In some embodiments, the main body 124, right cover 126, left cover 128,and the pins 138 a, 138 b, 138 c, 138 d, and 138 e are made by injectionmolding. After molding, the right and left covers 126 and 128 can beaffixed to the main body 124 using various techniques including, but notlimited to, ultrasonic welding, laser welding, solvent bonding, adhesivebonding, UV curable adhesive bonding, and the like. Various polymericmaterials can be used to construct the main body 124, right cover 126,left cover 128, and pins 138 a-e. For example, such polymeric materialscan include, but are not limited to acrylic, polycarbonate, polyvinylchloride (PVC), polyethylene, polypropylene, polymethyl methacrylate,polystyrene, acrylonitrile butadiene styrene (ABS), polyethylene,polypropylene, and the like, and combinations thereof. In someembodiments, the materials are used to construct the main body 124,right cover 126, left cover 128, and pins 138 a-e comprise anacrylic-based multi-polymer compound. In some embodiments, the main body124, right cover 126, and left cover 128 are essentially transparent, orat least translucent. Therefore, in FIG. 4, features of the main body124 are visible even though the right cover 126 is attached thereto.

In some embodiments, overmolding, such as by insert molding ormulti-shot molding techniques, may be used to construct some aspects ofthe main body 124, right cover 126, and/or left cover 128 (i.e., adevice component). For example, elastomeric valve elements (as describedfurther below) may be overmolded in the left cover 128. To generatevalves by overmolding, a first mask is used to generate a devicecomponent without valves. The mask is an inverse of the shape of thedevice component, the device component including open spaces for laterinsertion of valves. A polymer is poured into the first mask to form ahard plastic device component. Then a second mask having the inverse ofthe shape of the device component with the valves is provided. Thehardened plastic device component is placed in the mask, and anelastomeric material is injected into the open spaces formed in thedevice component by the first mask, thereby forming elastomeric valvesin the device component. In some embodiments, the device component isthe main body 124, right cover 126, and/or left cover 128. Exemplaryvalves 160 a-e, 168, and 170 in a left cover 128 formed by overmoldingare shown in FIG. 7. In some embodiments, the valves comprise anelastomeric material, deformable upon application of pressure.Deformation of the valves by application of external pressure pushes theelastomeric material into the duct, thereby fluidically sealing the ductto prevent flow of a sample liquid through the duct.

Further, in some embodiments secondary operations may be performed tothe cartridge 120. For example, one or more needles 123 a-b (refer toFIG. 6) for piercing a blood collection tube may be installed within thesample well 122 using secondary operations.

The single-use cartridge 120 also includes the five pins 138 a, 138 b,138 c, 138 d, and 138 e. The pins 138 a-e are individual component parts(e.g., refer to FIG. 10B) that are retained within openings of the mainbody 124 (e.g., within testing chambers 136 a-e (sometimes referred toas “cups”) as described further below in connection with FIGS. 8A-10B).Tabs 129, located on the right and left covers 126 and 128, mechanicallyretain the pins 138 a-e in the main body 124. However, the pins 138 a-eare free to move within the confines of the main body 124 to a limitedextent. For example, the pins 139 a-e are free to rotate uninhibitedlywithin the main body 124 and to translate vertically by few millimeters.This configuration of the pins 138 a-e in relation to the othercomponents of the cartridge 120 can be created as follows. Prior toaffixing the right and left covers 126 and 128 to the main body 124, thepins 138 a-e can be placed within their respective locations in the mainbody 124 as shown in FIG. 5. With the pins 138 a-e positioned in themain body 124, the right and left covers 126 and 128 can then be affixedto the main body 124. With the right and left covers 126 and 128 affixedto the main body and the pins 138 a-e positioned in the main body 124,the pins are secured in place vertically by the tabs 129 over the top ofthe pin 138 a-e such that they cannot fall out or be removed from thecup 136 a-e without removal of the right and left covers 126 and 128from the main body 124. The tabs 129 allow free rotational movement ofthe pin 138 a-e, as well as sufficient vertical motion to allow the pin138 a-e to interact with a fluid sample to perform a measurement ofviscoelastic characteristics of a fluid sample in the cup 136 a-e, e.g.,rotational thromboelastometry. In addition, the tabs 129 provide anopening for a shaft 310 b to couple with a pin 138 b, as shown in FIG.10C. In one example, the right and left covers 126 and 128 are affixedto the main body 124 and thereafter the pins 138 a-e are pushed into themain body 122 past the tabs 129. The tabs 129 of the right and leftcovers 126 and 128 will block the pins 138 a-e from falling out of themain body 122, even if the cartridge 120 is turned upside down. In someembodiments, the pin and tabs are positioned to prevent escape ofsemi-coagulated fluid sample in the testing chamber from escaping thetesting chamber, even if the cartridge 120 is turned upside down.

In some embodiments, the main body 124 includes a barcode location 125.The barcode location 125 can be used as a location at which to adhere abarcode label, or to print a barcode. The barcode location 125 is on theleading end of the cartridge 120 (in relation to the direction ofinsertion of the cartridge 120 into the analyzer console 140 as shown inFIGS. 1-3).

In the depicted embodiment, the right cover 126 includes blood detectionlocations 127 a and 127 b. As will be described further below, the blooddetection locations 127 a and 127 b are designated locations on thecartridge 120 at which sensors of the analyzer console 140 interfacewith the cartridge 120. The sensors inspect for the presence of bloodwithin the cartridge 120 at the blood detection locations 127 a and 127b. In some embodiments, the sensors are optical sensors (e.g., infraredsensors) and the blood detection locations 127 a and 127 b are polishedareas that have enhanced transparency and optical clarity. As such, theright cover 126 is configured so that the optical sensors of theanalyzer console 140 can readily detect the presence or absence of bloodat the blood detection locations 127 a and 127 b.

Referring now to FIGS. 4, 5, and 6, broadly speaking the single-usecartridge 120 is configured to: (i) extract blood from a bloodcollection tube (e.g., blood collection tube 10 of FIGS. 1-3) andmeasure a precise volume of the extracted blood, (ii) mix a preciseamount of blood with reagents, and (iii) deliver the mixture to multiplecup and pin locations of the cartridge 120 where thromboelastometrytesting is performed. These steps will be described in more detailbelow.

In the depicted embodiment, the single-use cartridge 120 includes fiveindividual blood flow channels 130 a, 130 b, 130 c, 130 d, and 130 e.Alternately, in some embodiments the cartridge includes a singleindividual blood flow channel, or two individual blood flow channels, orthree individual blood flow channels, or four individual blood flowchannels, or six individual blood flow channels, or more than sixindividual blood flow channels. Each channel 130 a-e includes: (i) ameasuring chamber, (ii) a mixing chamber containing reagent(s) and amixing element, and (iii) a blood coagulation testing chamber (e.g., inthis embodiment a cup having a movable probe/pin therein). For example,the channel 130 a includes a measuring chamber 132 a, a mixing chamber134 a, and a testing chamber 136 a (refer to the example of the testingchamber being depicted in detail in FIGS. 10A-B). Similarly, the channel130 b includes a measuring chamber 132 b, a mixing chamber 134 b, and atesting chamber 136 b; the channel 130 c includes a measuring chamber132 c, a mixing chamber 134 c, and a testing chamber 136 a; the channel130 d includes a measuring chamber 132 d, a mixing chamber 134 d, and atesting chamber 136 d; and the channel 130 e includes a measuringchamber 132 e, a mixing chamber 134 e, and a testing chamber 136 e.

In some embodiments, the sample well 122 includes needles 123 a and 123b that are configured to pierce a septum of a blood collection tube whenthe blood collection tube is inserted into the sample well 122. Theneedle 123 a is in fluid communication with the channels 130 a-e, whilethe needle 123 b is a vent that facilitates the ready flow of blood outof the blood collection tube.

In the depicted embodiment, the fluid flow paths from the needle 123 ato the channels 130 a-e are as follows. The needle 123 a is confluentwith the measuring chamber 132 a. The measuring chamber 132 a isconfluent with the measuring chamber 132 b. The measuring chamber 132 bis confluent with the measuring chamber 132 c. The measuring chamber 132c is confluent with the measuring chamber 132 d. The measuring chamber132 d is confluent with the measuring chamber 132 e. Accordingly, bloodcan flow out of the blood collection tube through the needle 123 a tothe measuring chamber 132 a; from the measuring chamber 132 a to themeasuring chamber 132 b; from the measuring chamber 132 b to themeasuring chamber 132 c; from the measuring chamber 132 c to themeasuring chamber 132 d; and from the measuring chamber 132 d to themeasuring chamber 132 e. The measuring chambers 132 a-e may also bereferred to as metering chambers 132 a-e. Each measuring chamber 132 a-ehas an inlet port and an outlet port. The inlet ports are located nearthe top of the measuring chambers 132 a-e. For example, measuringchamber inlet port 132 ai is located near the top of the measuringchamber 132 a. This configuration can be advantageous if the bloodcontains gaseous bubbles, because such gas may be allowed to escape fromthe blood as the blood enters the measuring chambers 132 a-e. Inaddition, this configuration may advantageously minimize fluid flowturbulence as the blood flows into the measuring chambers 132 a-e,thereby reducing the likelihood of damaging the blood cells.

The outlet ports 134 ao-eo for transferring blood from the measuringchambers 132 a-e to the mixing chambers 134 a-e are located at thebottom of the measuring chambers. For example, measuring chamber outletport 132 ao is located at the bottom of the measuring chamber 132 a. Insome embodiments, the bottom of the measuring chamber 132 a is angleddownward towards the outlet port 132 ao. In some embodiments, the bottomof the measuring chamber 132 a is at an angle of 2°-15° from a planeparallel to the bottom or top of the cartridge 120. In some embodiments,the bottom of the measuring chamber 132 a is at an angle of 2°-15° froma plane orthogonal to the direction of force applied to move the bloodsample through the outlet port 132 ao. In one embodiment, the anglesdescribed above are approximately 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, 10°,11°, 12°, 13°, 14°, or 15°. In a preferred embodiment, the anglesdescribed above are 5°, although other angles will also be effective.This configuration can help facilitate the complete filling of themeasuring chambers 132 a-e with blood. It can also minimize transfer ofbubbles into the outlet port 132 ao as more blood is transferred to theoutlet port 132 ao before the surface of the volume of blood (which maycontain bubbles) contained in the measuring chamber 132 a contacts theoutlet port 132 ao. As such, a precise volume of blood is containedwithin the measuring chambers 132 a-e.

In some embodiments, the top of the measuring chamber 132 a is angled tocause air to escape the measuring chamber 132 a from a transfer portlocated at the top of the measuring chamber opposite to the inlet port132 ai. The transfer port is used to transfer air and fluid out of themeasuring chamber 132 a and into another measuring chamber (e.g., 132 b)or into an overflow chamber 139. In this embodiment, the top of themeasuring chamber 132 a is angled upward from a low point above an inletport 132 ai to a higher point above the transfer port. The angle of thetop of the measuring chamber is between 2°-15° when compared to the aplane parallel to the bottom or top of the device, or as compared to aplane orthogonal to the major field of gravitational force applied tothe blood sample while in the measuring chamber 132 a. In oneembodiment, the angle described above is approximately 2°, 3°, 4°, 5°,6°, 7°, 8°, 9°, 10°, 11°, 12°, 13°, 14°, or 15°. In a preferredembodiment, the angle described above is 5°, although other angles willalso be effective. In a device comprising the angled top of themeasuring chamber 132 a, air and bubbles are transferred out of themeasuring chamber 132 a before blood, providing a measured blood samplewith decreased amount of air that may impact the accuracy of themeasurement of the blood, as well as interfere with other downstreamapplications. In some embodiments, both the top and bottom of themeasuring chamber 132 a are angled as described above.

From the foregoing description of the fluid flow paths from the needle123 a to the measuring chambers 132 a-e, and from the foregoingdescription of the location of the measuring chamber outlet ports, itshould be understood that the measuring chambers 132 a-e will be filledwith blood in a sequential manner. That is, first measuring chamber 132a will be filled with blood; then blood from measuring chamber 132 awill flow to measuring chamber 132 b; then measuring chamber 132 b willbe filled with blood; then blood from measuring chamber 132 b will flowto measuring chamber 132 c; then measuring chamber 132 c will be filledwith blood; then blood from measuring chamber 132 c will flow tomeasuring chamber 132 d; then measuring chamber 132 d will be filledwith blood; then blood from measuring chamber 132 d will flow tomeasuring chamber 132 e; then measuring chamber 132 e will be filledwith blood.

After the measuring chamber 132 e is filled with blood, then blood frommeasuring chamber 132 e will flow to an overflow chamber 139. The bloodflowing from measuring chamber 132 e will enter the overflow chamber 139at an overflow chamber inlet port 139 i. As will be described furtherbelow, the overflow chamber 139 serves to ensure that the measuringchamber 132 e becomes completely full, while preventing blood fromexiting the cartridge 120 and flowing into a vacuum source that is usedto draw the blood into the measuring chambers 132 a-e as describedabove. The vacuum source is fluidly connected to the overflow chamber139 at an overflow chamber outlet port 139 o. When a negative pressure(with respect to ambient pressure) from the vacuum source is applied atthe overflow chamber outlet port 139 o, blood from a blood collectiontube that is coupled with needle 123 a will flow into the cartridge 120to fill all the measuring chambers 132 a-e. Some blood will also exitthe measuring chamber 132 e and flow towards the overflow chamber 139.

As described further below, various valves and vents are interspersedwithin the fluid flow paths so that the blood flow can be controlled bythe analyzer console according to predefined schemes. In addition, theaforementioned blood detection locations 127 a and 127 b (refer to FIG.5) are designated locations on the cartridge 120 at which sensors of theanalyzer console 140 interface with the cartridge 120. The sensorsinspect for the presence of blood within the cartridge 120 at the blooddetection locations 127 a and 127 b. The blood sensor location 127 a ison the fluid flow path between the needle 123 a and the measuringchamber 132 a. When the analyzer console detects blood at blood sensorlocation 127 a, the analyzer console 140 determines that blood has beendrawn into the cartridge 120. The blood sensor location 127 b is on thefluid flow path between the measuring chamber 132 e and the overflowchamber 139. When the analyzer console detects blood at blood sensorlocation 127 b, the analyzer console 140 determines that blood has beendrawn into and filled all the measuring chambers 132 a-e. Further, whenthe analyzer console 140 detects blood at blood sensor location 127 b,the analyzer console 140 may cease further application of negativepressure at the overflow chamber outlet port 139 o. In other words, bydetecting blood at blood sensor location 127 b, the analyzer console 140can determine that the application of vacuum has successfully filled allthe measuring chambers 132 a-e and that the application of vacuum can beceased. Optionally, the cartridge 120 may be equipped with a bloodtemperature sensor at or near the location of blood sensor location 127b so as to verify the blood sample is at a predetermined targettemperature.

As described above, each individual channel 130 a-e has a measuringchamber 132 a-e respectively. In some embodiments, the fluid flow pathswithin the individual channels 130 a-e are as follows. From themeasuring chambers 132 a-e, the blood can flow to the respective mixingchambers 134 a-e. For example, the blood from measuring chamber 132 acan flow to the mixing chamber 134 a. Similarly, the blood frommeasuring chamber 132 b can flow to the mixing chamber 134 b; the bloodfrom measuring chamber 132 c can flow to the mixing chamber 134 c; theblood from measuring chamber 132 d can flow to the mixing chamber 134 d;and the blood from measuring chamber 132 e can flow to the mixingchamber 134 e. From the mixing chambers 132 a-e (after completion of themixing), the blood can flow to the respective testing chambers 136 a-e(having a corresponding probe/pin 138 a-e therein, refer below to FIG.10A-b). For example, the blood from mixing chamber 134 a can flow to thetesting chamber 136 a. Similarly, the blood from mixing chamber 134 bcan flow to the testing chamber 136 b; the blood from mixing chamber 134c can flow to the testing chamber 136 c; the blood from mixing chamber134 d can flow to the testing chamber 136 d; and the blood from mixingchamber 134 e can flow to the testing chamber 136 e. Various valves andvents that are controllable by the analyzer console 140 are interspersedwithin the fluid flow paths of the individual channels 130 a-e. Usingsuch valves and vents, the blood flow within the individual channels 130a-e can be controlled by the analyzer console 140 in accordance withpredefined schemes.

Referring now to FIGS. 6 and 7, additional features of the cartridge 120will now be described. In FIG. 6, a side view of particular chambers ofthe cartridge 120 (measuring chambers 132 a-e, reagent mixing chambers134 a-e, and blood coagulation testing chambers 136 a-e) is provided. InFIG. 7, a left side view of cartridge 120 and individual channels 130a-e is provided. In this view there is visibility of testing chamberinlet ports 136 ai, 136 bi, 136 ci, 136 di, and 136 ei for testingchambers 136 a-e respectively. The inlet ports 136 ai-ei are locatednear the top of the testing chambers 136 a-e, for example, along a sidewall of the chamber 136 a-e and at a height above the distal head of thepin 138 a-e that interacts with the blood sample but below the proximalend of the pin 138 a-e (refer to FIG. 10B). This configuration can beadvantageous if the blood contains gaseous bubbles, because such gas maybe allowed to escape from the blood as the blood enters the cups 136a-e. In viscous solutions, bubbles may be retained at the bottom of thecup 136 a-e if the solution enters through the bottom, adverselyimpacting thromboelastometric measurements by the pin 138 a-e in the cup136 a-e. In addition, this configuration may advantageously minimizefluid flow turbulence as the blood flows into the testing chambers 136a-e. Fluid flow turbulence and bubble mixing is also minimized by havinga small diameter or blood flow area of the sample inlet port 136 bi intothe cup 136 a-e. Bubbles present in blood from the mixing chamber 134a-e separate from the fluid and remain at the top surface of the bloodin the cup 136 a-e by using a smaller diameter of a sample inlet port136 bi in combination with the location of the inlet port 136 bi alongthe side wall of the chamber 136 a-e. In some embodiments, the diameterof the sample inlet port 136 bi is 1 mm. In some embodiments, thediameter of the sample inlet port 136 bi is approximately 0.5, 0.6, 0.7,0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 mm.

In the depicted embodiment, the cartridge 120 includes two locator pinreceptacles 140 a and 140 b. The locator pin receptacles 140 a and 140 bare used to mate with locator pins of the analyzer console 140 (asdescribed further below). In this manner, the cartridge 120 can beaccurately positioned in relation to the analyzer console 140.

The cartridge 120 also includes a vacuum application port 162. When asource of vacuum is applied at the vacuum application port 162, and whenthe vents and valves of the cartridge 120 are in the properconfiguration, blood can be drawn into the measuring chambers 132 a-e asdescribed above, and as described further below.

The cartridge 120 also includes a pressure application port 164. When asource of pressure is applied at the pressure application port 164, andwhen the vents and valves of the cartridge 120 are in the properconfiguration, blood can be forced to flow from the measuring chambers132 a-e into the mixing chambers 134 a-e, and subsequently from themixing chambers 134 a-e into the testing chambers 136 a-e as describedabove, and as described further below.

In the depicted embodiment, the cartridge 120 also includes vents 166 a,166 b, 166 c, 166 d, and 166 e. Other cartridge embodiments may includefewer or more vents. The vents 166 a-e are confluent with the mixingchambers 134 a-e respectively. Accordingly, when the vents 166 a-e areopen to allow airflow therethrough, air from the mixing chambers 134 a-ecan be readily displaced from the mixing chambers 134 a-e as blood flowsinto the mixing chambers 134 a-e. Conversely, when the vents 166 a-e areclosed to prevent airflow therethrough, blood is inhibited from flowinginto the mixing chambers 134 a-e because the air within the mixingchambers 134 a-e is not allowed to be displaced therefrom. The vents 166a-e can be individually opened and closed by the analyzer console 140 inaccordance with predefined schemes as described further below.Accordingly, blood flow into the mixing chambers 134 a-e can becontrolled as desired.

In the depicted embodiment, the cartridge 120 also includes valves 168,170, 160 a, 160 b, 160 c, 160 d, and 160 e. Other cartridge embodimentsmay include fewer or more valves. The valves 168, 170, and 160 a-e arelocated within fluid flow paths of the cartridge 120. Accordingly, thevalves 168, 170, and 160 a-e can be actuated (opened or closed) by theanalyzer console 140 to allow or to prevent fluid flow through the fluidflow paths in which the valves 168, 170, and 160 a-e are respectivelylocated. For example, the valve 168 is located in the fluid flow pathbetween the needle 123 a and the measuring chamber 132 a. Accordingly,when the valve 168 is open blood can flow from the needle 123 a to themeasuring chamber 132 a, and when the valve 168 is closed blood cannotflow from the needle 123 a to the measuring chamber 132 a.

The valve 170 is located in the fluid flow path between the measuringchamber 132 e and the overflow chamber 139. Accordingly, when the valve170 is open blood can flow from the measuring chamber 132 e to theoverflow chamber 139, and when the valve 170 is closed blood cannot flowfrom the measuring chamber 132 e to the overflow chamber 139.

The valves 160 a-e are located in the fluid flow paths between themixing chambers 134 a-e and the testing chambers 136 a-e respectively.Accordingly, when the valves 160 a-e are open blood can flow from themixing chambers 134 a-e to the testing chambers 136 a-e respectively,and when the valves 160 a-e are closed blood cannot flow from the mixingchambers 134 a-e to the testing chambers 136 a-e.

As will be described further below, in some embodiments the valves 160a-e can be individually actuated by pins that are translated towards andaway from the valves 160 a-e. To close the valves 160 a-e, the pins canengage with and distend elastomer members of the valves 160 a-e so thatthe elastomer member makes contact with a valve seat of the valves 160a-e. When such pins are retracted away from the elastomer members of thevalves 160 a-e, the elastomer members will rebound such that theelastomer member is no longer distended and then the valve is opened.The pins can be translated by solenoids in some embodiments.

Other mechanisms to regulate fluid flow in the cartridge 120 may also bepresent. For example, stop junctions may be placed between the measuringchamber 132 a-e and the mixing chamber 134 a-e to control the flow ofblood from the measuring chamber 132 a-e to the mixing chamber 134 a-e.In some embodiments, the stop junctions are a barrier that can be openedupon application of a sufficient amount of pressure to the barrier. Insome embodiments, the stop junction comprises a narrow area for flow ofthe sample fluid such that surface tension of the sample fluid preventsflow through the stop junction unless sufficient pressure is applied.Once sufficient pressure is applied, the flow of the sample fluidthrough the stop junction may continue due to capillary forces.

Referring to FIG. 6 in more detail, some embodiments of the mixingchambers 134 a-e contain: (i) one or more dissolvable reagent beads 180,(ii) multiple retaining elements 182, and (iii) a mixing element 184.The one or more reagent beads 180 are disposed within and retainedwithin the confines of the multiple retaining elements 182. The mixingelements 184 are disposed in the bottom portions of the mixing chambers134 a-e, and are free to move horizontally across the bottom portions ofthe mixing chambers 134 a-e. The multiple retaining elements 182separate the reagent beads 180 from the mixing element 184, and preventthe mixing element 184 from migrating upward away from the bottomportions of the mixing chambers 134 a-e. Thus, the multiple retainingelements 182 prevent direct contact of the mixing element 184 withreagent beads 180 in the mixing chambers 134 a-e. Preferably, theretaining elements 182 extend into each mixing chamber 134 a-e so as tomaintain a predetermined vertical position of each of the reagent beads180 within the mixing chamber (e.g., a vertical position below theheight of the blood portion passed into the mixing chamber 134 a-e),thereby ensuring that each of the beads 180 will be submerged when thepredetermined amount of blood is directed into the respective mixingchamber 134 a-e. In an embodiment, the height of the liquid that fillsthe mixing chamber 134 a-e from the measuring chamber 132 a-e (i.e., thefill level) is above the retaining elements 182 in the mixing chamber.In some embodiments, the retaining elements 182 are above the height ofthe fill level of the mixing chamber. In these embodiments, theretaining elements are configured to position the reagent in the path ofthe fluid such that the reagent is dissolved by the liquid upon entry ofthe liquid into the mixing chamber. In some embodiments, the flow pathis defined as the path the liquid travels to go from one chamber toanother, including within the chamber itself after entering from aninlet or duct.

Also, in some embodiments, the multiple retaining elements 182 in eachmixing chamber 134 a-e maintain each of the reagent beads 180 in therespective mixing chamber 134 a-e separate from one another. In suchembodiments, each of the reagent beads 180 is not contacted by otherbeads 180 in the respective mixing chamber 134 a-e, is not contacted bythe mixing element 184 in the respective mixing chamber 134 a-e, and ismaintained at a vertical height within the respective mixing chamber 134a-e below the height of the blood portion transported into therespective mixing chamber 134 a-e.

The retaining elements 182 may take the form of several uniqueconfigurations that result in control over the location of the reagentbeads 180. In some embodiments, the retaining elements 182 also preventcontact between different reagent beads 180, contact of reagent beads180 with the mixing element 184, and/or contact of the reagent beads 180with other surfaces or components in the mixing chamber 134 a-e. In someembodiments, the retaining element 182 is configured to limit movementof the reagent bead 180 within the mixing chamber 134 a-e and configuredto allow the sample liquid or blood sample to dissolve the reagent bead180. In some embodiments, the retaining element 182 comprises a barrier.The retaining element 182 can also comprise an inward protrusion or anoutward protrusion in the wall of the mixing chamber 134 a-e or on thesurface of a right cover 126 or left cover 128, or on other surfaces ofthe device. In some embodiments, the retaining element 182 comprises achannel, a post, or a divot. The retaining element 182 may comprise anarray of posts or an array of divots. In some embodiments, the array ofposts comprises posts of different diameters to hold reagent beads ofdifferent diameters. In some embodiments, the retaining element 182comprises a compartment or a series of compartments for holding areagent bead. The retaining element 182 can also be configured to bothlimit the movement of a reagent bead in the mixing chamber 134 a-e, andto allow blood to flow in a way that it contacts and dissolves thereagent bead 180. In some embodiments, the retaining element 182 isconfigured to allow flow of a blood sample through the mixing chamber134 a-e.

The retaining element 182 can further secure the reagent bead 180 belowa predetermined blood sample fill level in the mixing chamber 134 a-e.This fill level is determined by the volume of blood provided by themeasuring chamber 132 a-e, and by the dimensions of the mixing chamber134 a-e and volume of components or reagents within the mixing chamber134 a-e at the time of filling. This fill level can be predeterminedbased on the above factors. Therefore, the retaining elements 182 arespecifically designed to maintain the position of the reagent beads 180below this predetermined fill level.

Additionally, the retaining elements 182 can limit the movement of amixing element 184 within the mixing chamber 134 a-e. In someembodiments, the resting element 182 used to restrict movement of amixing element 184 within the mixing chamber 134 a-e comprise an arrayof posts or a compartment that allows a sample fluid or blood sample inthe mixing chamber 134 a-e to contact the mixing element 184 such thatthe sample fluid or blood sample is agitated to facilitate dissolvingreagents within the mixing chamber 134 a-e.

In the depicted embodiment, the one or more dissolvable reagent beads180 are spherical and are of two different sizes (e.g., about 2 mmdiameter and about 3 mm diameter). However, the use of other shapesand/or sizes of reagent beads 180 is also envisioned. In someembodiments, the reagent beads 180 are lyophilized materials, but otherforms of materials are also envisioned. The reagent beads 180 cancomprise materials such as, but not limited to, CaCl₂, ellagicacid/phospholipids, tissue factor, heparinase, polybrene, cytochalasinD, tranexamic acid, and the like, and combinations thereof. The reagentbeads 180 are dissolvable in blood. For example, in this particularembodiment, each of the five mixing chambers 134 a-e is configured tomix a predetermined volume of blood (as defined by the respectivemeasurement chamber 132 a-e) with a different reagent composition (fromthe one or more reagent beads 180 therein) for purposes of performingfive different assays. In this example, the first mixing chamber 134 emay include multiple reagent beads 180 the provide CaCl₂ and ellagicacid/phospholipids for mixing with the predetermined volume of blood(from the corresponding measuring chamber 132 e) so that the firstsample portion can be used in a first type of assay. Also in thisexample, the second mixing chamber 134 d may include multiple reagentbeads 180 the provide CaCl₂, ellagic acid/phospholipids, and heparinasefor mixing with the predetermined volume of blood (from thecorresponding measuring chamber 132 d) so that the second sample portioncan be used in a second type of assay. Further, in this example, thethird mixing chamber 134 c may include multiple reagent beads 180 theprovide CaCl₂, tissue factor, and polybrene for mixing with thepredetermined volume of blood (from the corresponding measuring chamber132 c) so that the third sample portion can be used in a third type ofassay. Also in this example, the fourth mixing chamber 134 b may includemultiple reagent beads 180 the provide CaCl₂, tissue factor, polybrene,and cytochalasin D for mixing with the predetermined volume of blood(from the corresponding measuring chamber 132 b) so that the fourthsample portion can be used in a fourth type of assay. Lastly, in thisexample, the fifth mixing chamber 134 a may include multiple reagentbeads 180 the provide CaCl₂, tissue factor, polybrene, and tranexamicacid for mixing with the predetermined volume of blood (from thecorresponding measuring chamber 132 a) so that the fifth sample portioncan be used in a fifth type of assay.

In some embodiments, the reagent bead 180 carrying the CaCl₂ reagent isseparated from the rest of the beads 180 in the respective mixingchamber 134 a-e so as to first allow mixing and then activation/clottingof the a citrated blood sample. Such separation of the reagent bead 180carrying the CaCl₂ reagent may be achieved using the retaining elements182 (as described above). Alternatively, such separation can be achievedby retaining the reagent bead 180 carrying the CaCl₂ reagent in aseparate channel or separate mixing chamber that is separated from otherbeads 180 in the respective chamber 134 a-e (such that the blood portionreaches the CaCl₂ reagent after the blood portion mixes with other beads180 within the respective mixing chamber 134 a-e). Alternatively, suchseparation can be achieved by positioning a CaCl₂ reagent liquid or adried-film CaCl₂ reagent in a separate channel so that the blood portionreaches the CaCl₂ reagent after the blood portion mixes with other beads180 in the respective mixing chamber 134 a-e. Alternatively, the reagentbead 180 carrying the CaCl₂ reagent can be coated with an extra layer(and then retained by the retained by the retaining elements 182 asdescribed above) so that the blood portion begins to dissolve thereagent bead 180 carrying the CaCl₂ reagent after the blood portionpreviously mixes with other beads 180 within the respective mixingchamber 134 a-e.

Other configurations for providing a reagent to the blood sample mayalso be used. In some embodiments, a reagent is coated on the wall of amixing chamber 134 a-e. In some embodiments, a reagent is coated on theright cover 126 or the left cover 128. The coated reagent on the rightcover 126 or the left cover 128 can be coated in a way that it will atleast partially or entirely be contained within the mixing chamber 134a-e. In some embodiments, the reagent is coated so that it remains underthe fill level of the mixing chamber 134 a-e (the fill level pertainingto the height of blood in the mixing chamber as determined in part bythe predetermined volume of blood as measured in the measuring chamber).In some embodiments, the coated reagent is a film layer, i.e., a reagentfilm. A reagent film is a layer of reagent coated on or near a surface.The reagent film may be liquid or may be dried. A liquid reagent may beretained as a film layer by a dissolvable layer of material placed overthe liquid reagent. A liquid reagent layer may also be applied and thendried on the surface. A pre-dried or solid film reagent may also beapplied to a surface to form a film layer. In some embodiments, the filmlayer is in the form of a dissolvable film strip. In some embodiments,certain reagents are preferred to be delivered in a reagent film asopposed to a reagent bead 180. For example, certain reagents that aredifficult to lyophilize in a reagent bead 180 may instead be applied onor near a surface in the device as a film layer.

In some embodiments, the coated reagent is in the form of reagent beads180. Reagent beads may be secured to the wall of a chamber or to a coverusing retaining elements 182. The retaining elements 182 may comprise aseries of compartments, posts, divots, inward or outward protrusions, oran array of any of the above. Other shapes or configurations of reagentthat can be coated or secured to the cover, a wall of a chamber, orwithin a fluidic passage between chambers, are also envisioned. In someembodiments, both reagent beads 180 and reagent film are coated on oneor more surfaces of the device, e.g., in the mixing chamber 134 a-e.

A reagent film may also be provided to dissolve in a blood sample in themixing chamber 134 a-e. The reagent film is dissolvable in blood. Thereagent film is adhered to a surface in the mixing chamber 134 a-e. Insome embodiments, a reagent film is deposited on the walls of the mixingchamber 134 a-e. In some embodiments, a reagent film is deposited on theright cover 126 or the left cover 128 at a region that at leastpartially covers or forms a wall of the mixing chamber 134 a-e. Thereagent film may be used alone, or in addition to one or more reagentbeads 180 placed in the mixing chamber 134 a-e. Thus, the use of one ormore reagent films in a mixing chamber 134 a-e provides additionalmechanisms of introducing a reagent into a mixing chamber 134 a-e todissolve in the blood.

In some embodiments, the reagent film comprises a lyophilized material,but other forms of materials are also envisioned. The reagent film cancomprise materials such as, but not limited to CaCl₂, ellagicacid/phospholipids, tissue factor, heparinase, polybrene, cytochalasinD, tranexamic acid, and the like, and combinations thereof. In oneparticular example, each of the five mixing chambers 134 a-e isconfigured to mix a predetermined volume of blood (as defined by therespective measurement chamber 132 a-e) with a different reagentcomposition (from one or more reagent beads 180 and/or one or morereagent films therein). In this example, the first mixing chamber 134 emay include multiple reagent beads 180 and at least one reagent film toprovide CaCl₂ and ellagic acid/phospholipids for mixing with thepredetermined volume of blood (from the corresponding measuring chamber132 e) so that the first sample portion can be used in a first type ofassay. Also in this example, the second mixing chamber 134 d may includemultiple reagent beads 180 and at least one reagent film to provideCaCl₂, ellagic acid/phospholipids, and heparinase for mixing with thepredetermined volume of blood (from the corresponding measuring chamber132 d) so that the second sample portion can be used in a second type ofassay. Further, in this example, the third mixing chamber 134 c mayinclude multiple reagent beads 180 and at least one reagent film toprovide CaCl₂, tissue factor, and polybrene for mixing with thepredetermined volume of blood (from the corresponding measuring chamber132 c) so that the third sample portion can be used in a third type ofassay. Also in this example, the fourth mixing chamber 134 b may includemultiple reagent beads 180 and at least one reagent film to provideCaCl₂, tissue factor, polybrene, and cytochalasin D for mixing with thepredetermined volume of blood (from the corresponding measuring chamber132 b) so that the fourth sample portion can be used in a fourth type ofassay. Lastly, in this example, the fifth mixing chamber 134 a mayinclude multiple reagent beads 180 and at least one reagent film toprovide CaCl₂, tissue factor, polybrene, and tranexamic acid for mixingwith the predetermined volume of blood (from the corresponding measuringchamber 132 a) so that the fifth sample portion can be used in a fifthtype of assay.

Further, a reagent film may be deposited on surfaces upstream ordownstream from the mixing chamber to mix with the blood sample beforeor after the mixing chamber. In some embodiments, a reagent filmcarrying the CaCl₂ reagent is placed in a separate channel or separatemixing chamber that is separated from other reagent beads 180 or reagentfilm in the respective chamber 134 a-e (e.g., such that the bloodportion reaches the CaCl₂ reagent film after the blood portion mixeswith other reagent beads 180 and/or reagent films within the respectivemixing chamber 134 a-e). Alternatively, a CaCl₂ reagent film may bedeposited in the mixing chamber 134 a-e and coated with an extradissolvable film layer so that the blood portion begins to dissolve theother reagent film carrying the CaCl₂ reagent after the blood portionpreviously mixes with other reagent beads 180 or reagent films withinthe respective mixing chamber 134 a-3.

In some embodiments, the reagent bead 180 or reagent film is separatedfrom the rest of the reagent beads 180 or reagent film in the respectivemixing chamber 134 a-e so as to allow mixing with different reagents ina preferred sequence. In one embodiment, such separation of the reagentbead 180 may be achieved using the retaining elements 182 (as describedabove). Alternatively, such separation can be achieved by retaining thereagent bead 180 or reagent film in a separate channel or separatemixing chamber that is separated from other beads 180 or reagent filmsin the respective chamber 134 a-e (such that the blood portion reachesand mixes with the loaded reagents in a preferred sequence). In oneembodiment, such separation can be achieved by positioning a reagentliquid, reagent bead 180 or a dried-film reagent in a separate channelso that the blood portion reaches the reagent before or after the bloodportion mixes with other reagent beads 180 or reagent films in therespective mixing chamber 134 a-e. In some embodiments, the reagent bead180 or reagent film is placed along a duct 134 ad fluidically connectingthe mixing chamber 134 a-e and the testing chamber 136 a-e.Alternatively, the reagent bead 180 or reagent film can be coated withan extra layer (and then retained by the retained by the retainingelements 182 as described above) so that the blood portion begins todissolve the reagent in the reagent bead 180 or reagent film comprisingan additional dissolvable layer after the blood portion previously mixeswith other reagent beads 180 or reagent films within the respectivemixing chamber 134 a-e. In some embodiments, the coated reagent layer isa dissolvable film layer manufactured from a substrate including apolymeric composition and a reagent. The polymeric composition forms adissolvable barrier to maintain the coating of the reagent on or near asurface in the device. Upon contact with a blood sample, the polymericcomposition dissolves to allow the blood sample to mix with the reagent.

The mixing element 184, comprises a ferromagnetic material including,but not limited to, nickel, cobalt, chromium (IV) oxide, gadolinium,permalloy, and alnico (an aluminum-nickel-cobalt alloy) and the like,and combinations thereof. In the depicted embodiment, the mixing element184 is spherical and is solid. In other embodiments, the mixing element184 may have a shape such as, but not limited to, cubical, conical,cylindrical, fan-shaped, elongated, prismatic, and the like, as well asirregular shapes. In some embodiments, the mixing element 184 mayinclude one or more surface features such as protrusions, indentations,or holes, and the like.

As will be described further below, the mixing elements 184 are movablewithin the mixing chambers 134 a-e in response to movement of magnetswith which the mixing elements 184 magnetically couple. The magnets thatthe mixing elements 184 magnetically couple with are contained withinthe analyzer console 140. The movement of the mixing elements 184encourages the reagent beads 180 to dissolve in the blood containedwithin the mixing chambers 134 a-e.

Referring now to FIGS. 8A-8H schematically depict an example fluidiccontrol process 200 that can be used with the thromboelastometry systemsprovided herein. The process 200 begins with blood contained only withinthe blood collection tube 10, and ends with blood/reagent mixturescontained in cups 136 a-e that are configured for rotarythromboelastometry. It should be understood that, in some embodiments,the cartridge 120 (refer to FIGS. 1-7) that is used to implement thefluidic control process 200 is heated (e.g., to about 37° C.) prior tohaving any blood therein.

Referring to FIG. 8A, the example fluidic control process 200 includesthe blood collection tube 10, the measuring chambers 132 a-e, the mixingchambers 134 a-e, and cups 136 a-e, the overflow chamber 139, the blooddetection locations 127 a and 127 b, the vacuum application port 162,the pressure application port 164, the vents 166 a-e, the valves 168,170, and 160 a-e. In the depicted configuration, valve 168 is closed,thereby retaining the blood substantially within the blood collectiontube 10.

While the example fluidic control process 200 includes five blood flowchannels (each comprising a measuring chamber 132 a-e, a mixing chamber134 a-e, and a cup 136 a-e respectively), it should be understood thathaving five blood flow channels is not required in all embodiments. Forexample, in some embodiments only a single blood flow channel isincluded. Alternately, two blood flow channels are included, or threeblood flow channels are included, or four blood flow channels areincluded, or six blood flow channels are included, or more than sixblood flow channels are included. Referring to FIG. 8B, the measuringchambers 132 a-e are filled with blood, and a small amount of blood iscontained within the overflow chamber 139. To arrive at this state, thefollowing changes were made (in comparison to FIG. 8A) and/or thefollowing conditions existed: (i) the valves 168 and 170 were opened,(ii) the valves 160 a-e were closed, (iii) the vents 166 a-e wereclosed, (iv) a negative pressure was applied to the vacuum applicationport 162, and (v) the pressure application port 164 was unpressurized.Accordingly, the blood flowed: (i) out of the blood collection tube 10,(ii) through the valve 168, (iii) through the blood detection location127 a, (iv) into and filling the measuring chamber 132 a, (v) into andfilling the measuring chamber 132 b, (vi) into and filling the measuringchamber 132 c, (vii) into and filling the measuring chamber 132 d,(viii) into and filling the measuring chamber 132 e, (ix) through blooddetection location 127 b, (x) through valve 170, and (xi) into theoverflow chamber 139. When blood was detected in the blood detectionlocation 127 b, the application of the negative pressure wasdiscontinued—thereby stopping further blood flow.

In some embodiments, the example fluidic control process 200 includes astop junction 132 as between one, some, or each of the measuringchambers 132 a-e and the mixing chambers 134 a-e. In some embodiments,blood flows through the stop junction 132 as in the duct 132 adconnecting the measuring chambers 132 a-e and the mixing chambers 134a-e through application of a positive pressure to the measuring chamberor a negative pressure to the mixing chamber 134 a-e. Stop junctionsprovide a mechanism to regulate flow without a connection to an externalcontrol device. The application of positive or negative pressure maycreate a pressure differential on either side of the stop junction,causing the stop junction to open, or drawing blood through the stopjunction by overcoming forces due to surface tension. The desiredpressure may be applied to cause blood to flow through the stop junctionvia pressure application port 164 and/or through opening an air pressurevent 166 a-e to release pressure in the corresponding mixing chamber 134a-e.

In some embodiments, the example fluidic control process 200 includes astop valve in lieu of or in addition to a stop junction between one,some, or each of the measuring chambers 132 a-e and the mixing chambers134 a-e. In some embodiments, the stop valve is a snap acting valve,snapping open upon reaching a set pressure, or a modulating valve thatopens in proportion to the pressure differential. Other cartridgeembodiments may include pressure-controlled valves in other fluid paths.

In some embodiments, the stop valve may be opened and closed by the samemechanism provided by the valves shown in the reaction system 168, 162,160 a-e at FIGS. 8A-8H. In some embodiments, the stop valves may beopened and closed through a mechanism other than pressure application tothe blood. In some embodiments, the stop valve is opened upon remotecommand from a control device connected to the stop valve. In someembodiments, the stop valve can be actuated by the analyzer console 140to allow or to prevent fluid flow through the fluid path from themeasuring chamber 132 a-e to the mixing chamber 134 a-e.

Referring to FIG. 8C, the measuring chambers 132 a-d are still filledwith blood, but the blood from the measuring chamber 132 e hastransferred to the mixing chamber 134 e. To arrive at this state, thefollowing changes were made (in comparison to FIG. 8B) and/or thefollowing conditions existed: (i) the valves 168 and 170 were closed,(ii) the valves 160 a-e remained closed, (iii) the vents 166 a-dremained closed, (iv) the vent 166 e was opened, and (v) a source of airpressure was applied to the pressure application port 164. Accordingly,the blood flowed: (i) out of the measuring chamber 132 e, and (ii) intothe mixing chamber 134 e. Because the vents 166 a-d and the valves 160a-d remained closed, the blood in the measuring chambers 132 a-d did notflow into the mixing chambers 134 a-d. With blood in the mixing chamber134 e, the mixing element in mixing chamber 134 e can move and agitatethe blood to facilitate the dissolving of the reagent beads therein.

In some embodiments, the fluidic control process 200 shown in FIG. 8Cincludes stop junctions (not shown) between the measuring chamber 132a-e and the mixing chamber 134 a-e to prevent the flow of blood from themeasuring chamber to the mixing chamber unless a sufficient pressuredifferential between the measuring chamber 132 a-e and the mixingchamber 134 a-e is applied. In this embodiment, the stop junctionprevents leakage of blood from measuring chambers 132 a-d into mixingchambers 166 a-d without opening the vents 166 a-d or applyingsufficient pressure to the pressure application port 164 to cause bloodto flow through the stop junction. To fill the measuring chamber 132 ewith blood from the mixing chamber 134 e, the following changes weremade (in comparison to FIG. 8B) and/or the following conditions existed:(i) the valves 168 and 170 were closed, (ii) the valves 160 a-e remainclosed, (iii) the vents 166 a-d remain closed, (iv) the vent 166 e wasopened, and (v) a source of air pressure was applied to the pressureapplication port 164 to cause blood to flow through the stop junctionfrom the measuring chamber 132 e into the mixing chamber 134 e, whilethe stop junctions between the measuring chambers 132 a-d and the mixingchambers 134 a-d prevent flow of blood from the measuring chambers 132a-d into the mixing chambers 134 a-d. With blood in the mixing chamber134 e, the mixing element in mixing chamber 134 e can move and agitatethe blood to facilitate the dissolving of the reagent beads therein.

Referring to FIG. 8D, the measuring chambers 132 a-d are still filledwith blood, and the blood/reagent mixture that was in the mixing chamber134 e (refer to FIG. 8C) has transferred to the cup 136 e. To arrive atthis state, the following changes were made (in comparison to FIG. 8C)and/or the following conditions existed: (i) the valves 168 and 170remained closed, (ii) the valve 160 e was opened, (iii) the valves 160a-d remained closed, (iv) the vent 166 e was closed (v) the vents 166a-d remained closed, and (vi) a source of air pressure was applied tothe pressure application port 164. Accordingly, the blood/reagentmixture flowed: (i) out of the mixing chamber 134 e, and (ii) into thecup 136 e. Because the vents 166 a-d and the valves 160 a-d remainedclosed, the blood did not flow from the measuring chambers 132 a-dtowards the mixing chambers 134 a-d. With the blood/reagent mixturelocated in the cup 136 e, rotary thromboelastometry can begin in the cup136 e.

Referring to FIG. 8E, the measuring chambers 132 a-c are still filledwith blood, the cup 136 e is still filled with blood/reagent mixture,and the blood that was in the measuring chamber 132 d (refer to FIG. 8D)has transferred to the mixing chamber 134 d. To arrive at this state,the following changes were made (in comparison to FIG. 8D) and/or thefollowing conditions existed: (i) the valves 168 and 170 remainedclosed, (ii) the valve 160 e was closed, (iii) the valves 160 a-dremained closed, (iv) the vent 166 d was opened (v) the vents 166 a-cand 166 e remained closed, and (vi) a source of air pressure was appliedto the pressure application port 164. In embodiments comprising a stopjunction between the measuring chamber 132 d and the mixing chamber 134d, the, blood travels through the stop junction by application ofpressure differential between the measuring chamber 132 d and the mixingchamber 134 d, while the stop junctions between the measuring chambers132 a-c and the mixing chambers 134 a-c prevent flow. Accordingly, theblood flowed: (i) out of the measuring chamber 132 d, and (ii) into themixing chamber 134 d. Because the vents 166 a-c and because the valves160 a-c remained closed, the blood did not flow from the measuringchambers 132 a-c towards the mixing chambers 134 a-c. With blood in themixing chamber 134 d, the mixing element in mixing chamber 134 d canagitate the blood to facilitate the dissolving of the reagent beadstherein.

Referring to FIG. 8F, the measuring chambers 132 a-c are still filledwith blood, the cup 136 e is still filled with blood/reagent mixture,and the blood/reagent mixture that was in the mixing chamber 134 d(refer to FIG. 8E) has transferred to the cup 136 d. To arrive at thisstate, the following changes were made (in comparison to FIG. 8E) and/orthe following conditions existed: (i) the valves 168 and 170 remainedclosed, (ii) the valve 160 d was opened, (iii) the valves 160 a-c and160 e remained closed, (iv) the vent 166 d was closed (v) the vents 166a-c and 166 e remained closed, and (vi) a source of air pressure wasapplied to the pressure application port 164. Accordingly, theblood/reagent mixture flowed: (i) out of the mixing chamber 134 d, and(ii) into the cup 136 d. Because the vents 166 a-c and the valves 160a-c remained closed, the blood did not flow from the measuring chambers132 a-c towards the mixing chambers 134 a-c. With the blood/reagentmixture located in the cup 136 d, rotary thromboelastometry can begin incup 136 d.

Referring to FIG. 8G, the measuring chambers 132 a-b are still filledwith blood, the cups 136 d-e are still filled with blood/reagentmixture, and the blood that was in the measuring chamber 132 c (refer toFIG. 8F) has transferred to the mixing chamber 134 c. To arrive at thisstate, the following changes were made (in comparison to FIG. 8F) and/orthe following conditions existed: (i) the valves 168 and 170 remainedclosed, (ii) the valve 160 d was closed, (iii) the valves 160 a-c and160 e remained closed, (iv) the vent 166 c was opened (iv) the vents 166a-b and 166 d-e remained closed, and (v) a source of air pressure wasapplied to the pressure application port 164. In embodiments comprisinga stop junction between the measuring chamber 132 c and the mixingchamber 134 c, the, blood travels through the stop junction byapplication of pressure differential between the measuring chamber 132 cand the mixing chamber 134 c, while the stop junctions between themeasuring chambers 132 a-b and the mixing chambers 134 a-b prevent flow.Accordingly, the blood flowed: (i) out of the measuring chamber 132 c,and (ii) into the mixing chamber 134 c. Because the vents 166 a-b andbecause the valves 160 a-b remained closed, the blood did not flow fromthe measuring chambers 132 a-b towards the mixing chambers 134 a-b. Withblood in the mixing chamber 134 c, the mixing element in mixing chamber134 c can agitate the blood to facilitate the dissolving of the reagentbeads therein.

Referring to FIG. 8H, the completion of the process 200 is depicted.That is, the cups 136 a-c all contain blood/reagent mixtures and rotarythromboelastometry can be taking place in the cups 136 a-e. This statecan be attained in accordance with the method of actuating the valves168, 170, and 160 a-e, and the vents 166 a-e, in conjunction withapplying vacuum to the vacuum application port 162 or pressure to thepressure application port 164 as described above.

Referring to FIG. 9, in some alternative embodiments, one or more of theindividual blood flow channels or paths can include multiple mixingchambers that are arranged in series. For example, the example fluidiccontrol process 280 includes five blood flow channels (similar to thenumber of channels in the embodiment of FIGS. 8A-H), but each of thechannels include two mixing chambers that are arranged in series (ratherthan a single mixing chamber for each respective mixing chamber like theembodiment of FIGS. 8A-H). That is, mixing chambers 137 a and 137 f arearranged in series between the measurement chamber 132 a and the cup 136a; mixing chambers 137 b and 137 g are arranged in series between themeasurement chamber 132 b and the cup 136 b; mixing chambers 137 c and137 h are arranged in series between the measurement chamber 132 c andthe cup 136 c; mixing chambers 137 d and 137 i are arranged in seriesbetween the measurement chamber 132 d and the cup 136 d; and mixingchambers 137 e and 137 j are arranged in series between the measurementchamber 132 e and the cup 136 e.

In some embodiments, the reagent bead carrying the CaCl₂ reagent isseparated from the other the reagent beads by locating the CaCl₂ reagentin the second of the two mixing chambers that are arranged in series. Inthat manner, the serial mixing chambers can allow the blood sample to bemixed with reagents and subsequently, at a controlled point in time,activation/clotting of the blood sample can be initiated.

While the example fluidic control process 280 includes five blood flowchannels that each include two mixing chambers that are arranged inseries, it should be understood that such a configuration is notrequired in all embodiments. For example, in some embodiments only asingle blood flow channel that includes two mixing chambers that arearranged in series is included in a cartridge. Such a single blood flowchannel with two mixing chambers may be the only blood flow channel inthe cartridge, or may be combined in a cartridge with one or more otherblood flow channels that include a single mixing chamber. It should beunderstood that all combinations and permutations of number of bloodflow channels and mixing chambers are included within the scope of thisdisclosure.

Turning now to the blood coagulation testing chambers 136 a-e in moredetail, the chambers 136 a-e can be configured to provide viscoelastictesting on the blood sample portion drawn into each chamber. Referringto FIGS. 10A and 10B, the pins 138 a-e are located in the cartridge 120.A representative example showing the pin 138 b located in the cup 136 billustrates that a clearance space exists between the outer diameter ofthe pin 138 b and the inner diameter of the cup 136 b. A blood/reagentmixture will at least partially fill the clearance space when rotarythromboelastometry is being performed therein. The pin 138 b has ashoulder 138 bs. The clearance space between the outer diameter of thepin 138 b and the inner diameter of the cup 136 b is less in the areasbelow the shoulder 138 bs than in the areas above the shoulder 138 bs.The areas between the outer diameter of the pin 138 b and the innerdiameter of the cup 136 b that are below the shoulder 138 bs are theareas that are active in regard to performing rotary thromboelastometry.

The cup 136 b and pin 138 b are shown in cross-section in FIG. 10B (inaccordance with section 10B-10B of FIG. 10A). In addition, a sampleinlet port 136 bi (located behind pin 138 b in the orientation of FIG.10B) is provided so that the blood/reagent mixture will flow into thecup 136 b via the sample inlet port 136 bi. In the depicted embodiment,the cup inlet port 136 bi is located in a sidewall of cup 136 b at aheight above the widened distal portion (refer to shoulder 138 bs) ofthe pin 138 b but below the proximal end of the pin 138 b (refer to endnear the entry to the axial bore 138 bb of the pin 138 b). In thisconfiguration, the blood/reagent mixture will flow into the cup 136 b soas to reduce the potential for bubble formation. In addition, locatingthe cup inlet port 136 bi near the top of cup 136 b eliminates theeffects that the cup inlet port 136 bi may otherwise have on thethromboelastometry measurements performed in the cup 136 b if the cupinlet port 136 bi is located in the active space between the innerdiameter of the cup 136 b and the outer diameter of the pin 138 b belowthe shoulder 138 bs.

In certain devices, bridging or other structure formation between thecup inlet port 136 bi (in the interior diameter of the cup 136 b) andthe outer diameter of the pin 138 b (i.e., the probe element) may occur.This may affect the ability of blood to flow into the cup 136 a-e, ormay cause error in the thromboelastometry measurements taken in the cup136 a-e. In some embodiments, the opening of the inlet port 136 bi andthe outer diameter of the pin 138 b are at least a minimum clearancedistance apart that prevents stable bridging of the blood sample orother coagulation structure formation between the pin 138 b and the cupinlet port 136 bi. At the minimum clearance distance, bridging betweenthe sample inlet port and the pin may still occur upon filling thetesting chamber, however, the bridge will not be stable enough topersist during measurement. Typically, a bridge will form around abubble, which will be instable if the diameter is equal to or greaterthan the minimum clearance distance. In some embodiments, a stablebridge is one that lasts longer than 1 second, 2 seconds, 3 seconds, 4seconds, or 5 seconds. In some embodiments, the minimum clearancedistance is at least 1.5 mm. In some embodiments, the minimum clearancedistance is at least 1.5 mm, 2 mm, 2.5 mm, or 3 mm. In the depictedembodiment in FIG. 10B, the cup inlet port 136 bi is located in asidewall of cup 136 b at a height above the widened distal portion(refer to shoulder 138 bs) of the pin 138 b but below the proximal endof the pin 138 b (refer to end near the entry to the axial bore 138 bbof the pin 138 b), and the inlet port 136 bi is at least 1.5 mm from thepin 138 b. In other words, the geometry of the pin can allow for thisadditional clearance since the pin has a narrower portion at thelocation at which the bridging might occur, thereby allowing for agreater clearance between the pin and the cup to prevent stablebridging.

In the depicted embodiment, the top of the cartridge 124 includes a vent121. The vent 121 is in fluid communication with the needle 123 b.Therefore, when air for venting a blood sample tube located in samplewell 122 is needed, air is drawn through the vent 121 and channeled intothe blood sample tube via the needle 123 b.

Each of the pins 138 a-e includes an axial bore. For example, the pin138 b includes an axial bore 138 bb. The axial bore 138 bb can be usedto engage with a shaft (not shown in FIG. 10B) for performing rotarythromboelastometry.

Referring to FIG. 10C, an example rotary thromboelastometry assembly 300b can engage with the pin 138 b to perform rotary thromboelastometry ona blood sample contained in the cup 136 b. In this particularembodiment, the example rotary thromboelastometry assembly 300 bincludes a baseplate 302, a shaft 310 b, a bearing 312 b, a mirror 314b, a counterforce spring 320 b, a light source 330 b, and a detector 340b (e.g., a charge-coupled device or the like). The baseplate 302 can belowered, as represented by arrows 318 b, such that a tip portion of theshaft 310 b enters the bore 138 bb to become releasably coupled with thepin 138 b. The bearing 312 b is engaged with the baseplate 302 and theshaft 310 b to facilitate rotational movement of the shaft 310 b inrelation to the baseplate 302. The counterforce spring 320 b is coupledto the shaft 310 b and oscillation of the spring 320 b can induce theshaft 310 b to oscillate back and forth by about +/−5° as represented byarrow 316 b. The mirror 315 is coupled to the shaft 310 b. The lightsource 330 b is configured to project light towards the mirror 314 b,and light can be reflected from the mirror 315 towards the detector 340b (depending on the rotational orientation of the shaft 310 b).Accordingly, the motion of the pin 138 b is detected by an opticaldetection system. It should be understood that other configurations ofthe rotary thromboelastometry assembly 300 b are also envisioned withinthe scope of this disclosure.

The detected motion data is analyzed by an algorithm running on theanalyzer console 140 (refer to FIGS. 1-3) to process and determine thethromboelastometry results. This system facilitates variousthromboelastometry parameters such as, but not limited to, clottingtime, clot formation time, alpha angle, amplitude, maximum clotfirmness, lysis onset time, lysis time, lysis index (%), and maximumlysis (%).

As the blood in the cup 136 b begins to coagulate, the motion amplitudeof the shaft 310 b starts to decrease (as detected by the deflection ofthe light beam from mirror 315 towards the detector 340 b). Duringcoagulation, the blood's fibrin backbone (together with platelets)creates a mechanical elastic linkage between the surfaces of the cup 136b and the pin 138 b. A proceeding coagulation process induced by addingone or more of the aforementioned activating factors can thus beobserved and quantified. In this way, various deficiencies of apatient's hemostatic status can be revealed and can be interpreted forproper medical intervention. At the end of the test process, thebaseplate 302 can rise to uncouple the shaft 310 b from the pin 138 b.

Referring to FIG. 11, the main chassis 144 of the analyzer console 140can include a front portion 144 f and a rear portion 144 b. In someembodiments, the rear portion 144 b houses at least some of the computerand electronic components that are necessary for the operations of theanalyzer console 140. For example, the rear portion 144 b can househardware devices and software such as, but not limited to, computerprocessors, memory devices, an operating system and other executableinstructions, power source(s), user interface controls, communicationdevices, circuit boards, and the like.

In the depicted embodiment, the front portion 144 f includes a cover 145and a sample handler assembly 400. The sample handler assembly 400defines an interior space in which the cartridge 120 can be received. Insome embodiments, the sample handler assembly 400 is a modularsub-assembly of the analyzer console 140, and the sample handlerassembly 400 can be readily removed from the analyzer console 140 forservice. The sample handler assembly 400 is electrically interconnectedwith the computer and electronic components that are housed in the rearportion 144 b. As such, the analyzer console 140 can perform rotarythromboelastometry on a blood sample located in cartridge 120 anddisplay the results on the touchscreen display 142.

Referring now to FIGS. 11 and 12, the analyzer console 140 can include acartridge receiver and clamp 410 and a viscoelastic measurement system480. A mechanical frame assembly is used to support the cartridgereceiver and clamp 410 and the viscoelastic measurement system 480 inorientations such that the cartridge receiver and clamp 410 and theviscoelastic measurement system 480 can function symbiotically.

Portions of the cartridge receiver and clamp 410 and the viscoelasticmeasurement system 480 are moveable in relation to the mechanical frameassembly (which is stationary in relation to the analyzer console 140).For example, the viscoelastic measurement system 480 can move upward anddownward. As will be described further below, the viscoelasticmeasurement system 480 can move downward to engage with the cartridge120 (e.g., refer to FIG. 11), and upward to disengage from the cartridge120. A portion of the cartridge receiver and clamp 410 can movehorizontally in relation to the mechanical frame assembly. As will bedescribed further below, a portion of the cartridge receiver and clamp410 can move horizontally to clamp or unclamp the cartridge 120 withinthe sample handler assembly 400.

In some embodiments, the cartridge receiver and clamp 410 includes amovable block sub-assembly and a stationary block sub-assembly. A spaceexists between the movable block sub-assembly and the stationary blocksub-assembly in which the cartridge 120 can be received. The movableblock sub-assembly can be translated towards or away from the stationaryblock sub-assembly. Accordingly, the cartridge 120 can be clamped andunclamped between the movable block sub-assembly and the stationaryblock sub-assembly by virtue of the relative movement therebetween. Insome embodiments, the viscoelastic measurement system 480 is mounted tothe movable block sub-assembly. Therefore, as the movable blocksub-assembly is translated, the viscoelastic measurement system 480 isalso translated.

In some embodiments, the moveable block sub-assembly can be translatedby an electric motor. In particular embodiments, the motor is a steppermotor. In some embodiments, a gear reducer is coupled to the motor.Using a belt and pulley arrangement for compactness, the motor can beused to drive a lead screw. The threads of the lead screw can be engagedwith complementary threads of the movable block such that a rotation ofthe lead screw results in horizontal translation of the movable block.In some embodiments, end-of-travel detectors (e.g., proximity sensors,optical sensors, micro-switches, and the like) are included to detectwhen the moveable block sub-assembly has been horizontally translated tothe desired end-of-travel positions.

In some embodiments, one or more springs can extend between the movablemoveable block sub-assembly and the stationary block sub-assembly. Thesprings can help facilitate a suitable clamping force between themovable block sub-assembly and the stationary block sub-assembly. Insome embodiments, the springs are adjustable.

In some embodiments, portions of the moveable block sub-assembly and thestationary block sub-assembly that make contact with the cartridge 120comprise a flexible or compressible material so that while the cartridge120 is clamped it is also protected from damage.

In particular embodiments, the moveable block sub-assembly can includeone or more features on the clamping face of the moveable blocksub-assembly that serve to position the cartridge 120 in the desiredlocation within the sample handler assembly 400. For example, in someembodiments the moveable block sub-assembly includes two locator pinsthat can mate with the locator pin receptacles 140 a and 140 b of thecartridge 120 (refer to FIG. 7) to accurately position the cartridge 120in relation to the sample handler assembly 400.

In some embodiments, one or both of the moveable block sub-assembly andthe stationary block sub-assembly include heating devices 412 that canwarm the cartridge 120 when the cartridge 120 is clamped therebetween.For example, in some embodiments the heaters 412 are electricalresistance heaters that are used to heat at least portions of thecartridge 120. In some embodiments, the heaters 412 are configured tofacilitate warming of individual portions of the cartridge 120independently from other portions of the cartridge 120. For example, oneor more of the individual blood flow channels 130 a, 130 b, 130 c, 130d, and 130 e (refer to FIGS. 4-7) can be independently warmed in somesuch embodiments. Warming may be performed to one or more sides of thecartridge 120. Other types of warming modalities may be used including,but not limited to, IR, ultrasonic, microwave, and the like.

In particular embodiments, one or more temperature sensors 414 areincluded that can detect the temperature of the cartridge 120 at one ormore locations on the cartridge 120. For example, in some embodimentsthe one or more temperature sensors 414 can be thermocouples,thermistors, infra-red temperature sensors, and the like. Accordingly,the analyzer console 140 can control the heating of the cartridge 120 toa predetermined temperature (e.g., about 37° C.) using the heaters 412and the temperature sensors 414.

The moveable block sub-assembly can include multiple solenoids that areused to actuate the aforementioned vents and valves of the cartridge120. For example (referring also to FIG. 7), the valves 168, 170, and160 a-e, can be actuated by valve actuators 430 and the vents 166 a-ecan be actuated by vent actuators 432. In some embodiments, the valveactuators 430 and the vent actuators 432 comprise solenoids. Actuationof the valves 168, 170, and 160 a-e by the valve actuators 430 can beaccomplished by coupling pins to the valve actuators 430 that areextendable from the moveable block sub-assembly to make contact with andto distend valve elastomer members so that the elastomer members makecontact with a valve seat within the cartridge 120. Actuation of thevents 166 a-e by the vent actuators 432 can be accomplished by couplingpins with resilient tips that are extendable from the moveable blocksub-assembly to obstruct the vents 166 a-e. Such pins with resilienttips can act as stoppers to substantially prevent airflow through thevents 166 a-e. In some embodiments, the valve actuators 430 and the ventactuators 432 comprise solenoids that include internal springs thatcause the valve actuators 430 and the vent actuators 432 to be normallyextended (e.g., when the electrical power is removed from thesolenoids). Accordingly, such normally closed solenoids will close thevents and valves of the cartridge 120 as a default configuration.

The sample handler assembly 400 also includes pressure source 436 andvacuum source 434 by which air pressure and vacuum can be applied to thepressure application port 164 and the vacuum application port 162 ofcartridge 120 respectively (refer to FIG. 7). For example, the pressuresource 436 and vacuum source 434 can make contact with the cartridge 120and can convey pressure or vacuum to the pressure application port 164and the vacuum application port 162 when the cartridge 120 is clampedwithin the cartridge receiver and clamp 410. The pressure source 436 andvacuum source 434 are at least partially made of a resilient material insome embodiments. For example, in some embodiments the pressure source436 and vacuum source 434 are at least partially made of a resilientmaterial such as, but not limited to, silicone, butyl rubber, nitrilerubber, ethylene propylene rubber, fluoroelastomers, and the like. Oneor more internally-housed pressure and/or vacuum pumps (not shown) canalso be included in the analyzer console 140. Such internally-housedpressure and vacuum pumps can be used to generate the air pressure orvacuum that is applied to the cartridge 120 to induce the transport ofblood within the cartridge 120 as described above in reference to FIGS.8A-8H.

As previously described, the cartridge receiver and clamp 410 alsoincludes the stationary block sub-assembly. In some embodiments, thestationary block sub-assembly does not move in relation to themechanical frame assembly and in relation to the analyzer console 140 asa whole.

In some embodiments, the analyzer console 140 includes a mixing unit440. In particular embodiments, the mixing unit 440 includes a motor, acrank and connecting rod assembly, and a magnet shuttle. Thesecomponents can be used to magnetically couple with the mixing elementsof the cartridge 120 and to induce movement of the mixing elementswithin the mixing chambers 134 a-e. The movement of the mixing elementsencourages the reagent beads to dissolve in the blood contained withinthe mixing chambers 134 a-e as described above.

The analyzer console 140 can also include one or more sensors 448. Theone or more sensors 448 can be used to detect the presence of blood inparticular locations within the cartridge 120, such as blood detectionlocations 127 a and 127 b as described above (refer to FIG. 5). In someembodiments, the sensors 448 are optical sensors, such as IR (infrared)sensors. In some embodiments, the sensors 448 can be used to detectblood in other areas of the cartridge 120, such as, but not limited to,in the cups 136 a-e (refer to FIGS. 8A-8H).

The sample handler assembly 400 of the analyzer console 140 alsoincludes the viscoelastic measurement system 480. The viscoelasticmeasurement system 480 includes the baseplate 302 (e.g., refer to FIG.10C), one or more thromboelastometry assemblies (e.g.,thromboelastometry assembly 300 b), and a linear actuator assembly. Theone or more thromboelastometry assemblies can each be affixed to thebaseplate 302. In some embodiments, the linear actuator assembly can becoupled to the baseplate 302 and to the cartridge receiver and clamp410. Accordingly, actuation of the linear actuator assembly cantranslate the baseplate 302 and the cartridge receiver and clamp 410towards each other or away from each other. A linear bearing assembly ofthe linear actuator can guide the baseplate 302 in a linear path, andstabilize the baseplate 302, as the baseplate 302 translates towards oraway from the cartridge receiver and clamp 410.

In some embodiments, the linear actuator assembly causes the baseplate302 to vertically raise or lower in relation to the cartridge receiverand clamp 410 using a motor (e.g., a DC motor or a stepper motor) thatrotates a lead screw that has threads that are engaged with a drive nut.The drive nut is coupled to the baseplate 302. In some embodiments,end-of-travel detectors (e.g., proximity sensors, optical sensors,micro-switches, and the like) are included to detect when the baseplate302 has been vertically translated to the desired end-of-travelpositions.

The viscoelastic measurement system 480 includes one of more rotarythromboelastometry assemblies (e.g., rotary thromboelastometry assembly300 b of FIG. 10C) that include a shaft configured to couple with a pin(e.g., the shaft 310 b configured to couple with the pin 138 b). Becausethe thromboelastometry assemblies are mounted to the baseplate 302, theshafts are raised or lowered in conjunction with the raising or loweringof the baseplate 302. Accordingly, actuation of the linear actuatorassembly causes the shafts to vertically raise or lower in relation tothe cartridge receiver and clamp 410, and in relation to a cartridge 120when a cartridge 120 is clamped within the cartridge receiver and clamp410. Therefore, from the description herein it can be understood thatactuation of the linear actuator assembly can engage and disengage theshafts from the pins of the cartridge 120 (e.g., refer to FIG. 10C thatshows baseplate 302 being lowered to engage shaft 310 b with pin 138 b).

In addition to the aforementioned features of the analyzer console 140,in some embodiments the analyzer console 140 also includes one or moreof the following features. The analyzer console 140 can include one ormore barcode scanners 450 that, for example, can read a barcode at thebarcode location 125 on the leading end of cartridge 120 (refer to FIG.5). In some embodiments, the analyzer console 140 can include one ormore devices to detect the presence of the cartridge 120 in a desiredinsertion location and/or orientation. For example, in some embodimentsone or more micro switches can be used to detect when the cartridge 120has been inserted in a desired location and orientation within thesample handler assembly 400. In some embodiments, the analyzer console140 can include one or more auxiliary connections 460. The auxiliaryconnections 460 can include network and device connectors such as, butnot limited to, one or more USB ports, Ethernet ports (e.g., RJ45), VGAconnectors, Sub-D9 connectors (RS232), and the like. Such auxiliaryconnections 460 can be located on the rear of the main chassis 144, orat other convenient locations on the main chassis 144. For example, insome embodiments one or more USB ports may be located on or near thefront of the main chassis 144.

The analyzer console 140 also includes a user interface 142 (e.g., witha touchscreen display in this embodiment). In the depicted embodiment,the user interface 142 is configured to receive user input and todisplay output information to the user. For example, the user can enterinformation to the analyzer console 140 by making selections of varioussoft-buttons that may be displayed on the user interface 142 at timesduring the beginning, middle, and end of the testing process. In someembodiments, other selections such as, but not limited to, soft keyboardentries can be provided via user interface 142. In some embodiments,data entry can be performed additionally or alternatively by voiceentry. In some embodiments, the user interface may include otherperipheral devices (e.g., a mouse, a keyboard, an additional displaydevice, and the like) as part of the analyzer console 140. In someembodiments, a computer data network (e.g., intranet, internet, LAN,etc.) may be used to allow for remote devices to receive and/or inputinformation from the system 100. For example, in some embodiments one ormore remote displays can be utilized via auxiliary connections 460. Inthe depicted embodiment, the user interface 142 also includes anexternal barcode reader 146 (refer to FIG. 1A). Alternatively oradditionally, the user interface 142 of the analyzer console 140 can beequipped with a reader configured to read near-field communication tags,RFID tags, or the like. The analyzer console 140 can also include one ormore control systems 470 that can execute instructions embodied in acomputer program. The control systems 470 can include, by way ofexample, both general and special purpose microprocessors, and any oneor more processors of any kind of digital computer. In some embodiments,the control systems 470 includes one or more such processors, memory,storage devices, interfaces, and other types of electronic sub-systemsand components. Such components may be mounted on a common motherboardor in other manners as appropriate. The control systems 470 can processinstructions for execution within the analyzer console 140, includinginstructions stored in the memory or on the storage device. In someimplementations, multiple processors and/or multiple buses may be used,as appropriate, along with multiple memories and types of memory. Also,multiple computing devices may be connected, with each device providingportions of the necessary operations (e.g., as a server bank, a group ofblade servers, or a multi-processor system).

The storage devices are capable of providing mass storage for thecontrol systems 470. In some implementations, the storage device may beor contain a computer-readable medium, such as a floppy disk device, ahard disk device, an optical disk device, or a tape device, a flashmemory or other similar solid state memory device, or an array ofdevices, including devices in a storage area network or otherconfigurations. A computer program product can be tangibly embodied inan information carrier. The computer program product may also containinstructions that, when executed, perform one or more methods, such asthose described above in reference to FIGS. 8A-8H. The computer programproduct can also be tangibly embodied in a computer- or machine-readablemedium, such as the memory, the storage device, or memory on theprocessor(s).

Referring to FIG. 13, in some implementations a user can interact withthe thromboelastometry systems provided herein according to an exampleprocess 490. In step 492, the user can insert a cartridge into ananalyzer console. In some examples, at least a portion of the cartridgeremains exposed while other portions of the cartridge are concealedwithin the analyzer console. For example, this step is exemplified abovein reference to FIG. 1A. In step 494, the user can couple a blood samplecontainer to the cartridge after a prompt is received from the analyzerconsole. Step 494 can be performed while the cartridge remains insertedin the analyzer console as defined by step 492. At step 496, the usercan press a “start” button (or equivalent) to initiate an automatedtransport of blood in the blood sample reservoir to the blood testingchambers of the cartridge such that the viscoelastic characteristics ofthe blood can be measured. In some examples, the analyzer consoleprovides an indication that the testing is ready to be initiated, butthat indication is not required as part of process 490.

Referring to FIGS. 14A and 14B, in some implementations athromboelastometry system can perform thromboelastometry according to anexample process 500. The individual steps of the process 500 may notnecessarily be performed in the order listed. Further, in someimplementations some steps of the process 500 may be performed inparallel. The process 500 may be performed by the thromboelastometrysystems described above, such as thromboelastometry system 100.

In step 510, the presence of a cartridge is detected in a receptacle ofan analyzer console of the thromboelastometry system. For example, thedetection may be performed by a micro switch, optical sensor, barcodescanner, and the like, or a combination thereof. Even though thecartridge is detected in the receptacle, at least a portion of thecartridge may be exterior to the analyzer console.

In step 520, the analyzer console actuates a clamping mechanism to clampthe cartridge at least partially in the analyzer console. For example,the cartridge receiver and clamp 410 as described above can be activatedto clamp the cartridge.

In step 530, the analyzer console can optionally determine if thecartridge has characteristics that indicate the cartridge has been usedpreviously. For example, the analyzer console may use optical sensors toinspect for the presence of blood in the cartridge. In some embodiments,if one or more characteristics that indicate the cartridge has been usedpreviously are detected, the analyzer console may suspend further stepsof process 500 and provide a pertinent message via the user interface.

In step 540, the analyzer console can perform one or more QC tests totest the integrity of the cartridge. For example, in some embodimentsthe cartridge can be tested for leaks such as by performing apressure/vacuum decay test.

In step 550, the analyzer console scans the cartridge for a barcode. Forexample, the analyzer console may scan a leading end of the cartridge atwhich a 1D or 2D barcode may be present.

In step 560, the analyzer console determined the types ofthromboelastometry assays to be performed based on the informationattained from the scan of the barcode in step 550.

In step 570, the shafts of the thromboelastometry sub-system of theanalyzer console are coupled with pins of the cartridge. The pins arelocated in cups of the cartridge. Accordingly, the coupling of theshafts of the thromboelastometry sub-system to the pins can configurethe thromboelastometry system to be capable of performingthromboelastometry on a blood sample contained within the cups of thecartridge. For example, referring to FIG. 10C, the shaft 310 b of thethromboelastometry assembly 300 b can be lowered towards the cartridgeso that the shafts 310 b become friction-fit and releasably coupled withthe pins 138 b of the cartridge 120.

In step 580, the analyzer console can begin rotatory reciprocation ofthe pins in relation to the cups of the cartridge. For example, thisstep is exemplified above in reference to FIG. 10C.

In step 590, the analyzer console can heat the cartridge. In someimplementations, the analyzer console may heat the cartridge to apredetermined temperature. In particular implementations, the analyzerconsole may maintain the cartridge at the predetermined temperature. Forexample, in some implementations the predetermined temperature may beabout 35° C. to about 40° C., and preferably about 37° C.

In step 600, the analyzer console provides a prompt to couple a bloodsample container to the cartridge. This prompt may be provided, forexample upon the successful completion of one or more steps, or upon thesuccessful verification of one or more conditions, or both. For example,this prompt may be provided upon the cartridge's successful attainmentof the predetermined temperature as per step 590, among other things.The prompt may be provided via the user interface of the analyzerconsole. For example, the prompt may be a visual message displayed on atouchscreen monitor of the analyzer console. An audible prompt may beprovided in some implementations.

In step 610, the analyzer console may optionally detect the presence ofblood in the cartridge. Such detection may be performed, for example,using one or more IR sensors of the analyzer console. The detection ofblood in the cartridge in this step can indicate that a blood samplecontainer was successfully coupled to the cartridge.

In step 620, the analyzer console can provide a prompt to “start”testing. In some implementations, the prompt to “start” testing may beprovided on the basis of the successful completion of one or more steps,or upon the successful verification of one or more conditions, or both.The prompt may be provided via the user interface of the analyzerconsole. For example, the prompt may be a visual message displayed on atouchscreen monitor of the analyzer console. In some embodiments, thetouchscreen can receive a user input to start the testing.

In step 630, the analyzer console can cause blood to flow from thesample container into the cartridge. In some implementations, a vacuumsource of the analyzer console is used to cause blood flow into thecartridge. In some implementations, an air pressure source of theanalyzer console is used to cause blood flow into the cartridge. Theanalyzer console may also actuate various valves or vents to control theblood flow within the cartridge (e.g., refer to FIGS. 8A-8H).

In step 640, the analyzer console can induce agitation to assist withthe dissolving of reagents in the blood contained within the cartridge.This step is exemplified above in regard to the horizontal reciprocationof the magnet shuttle with its one or more magnets that are magneticallycoupled with mixing elements of the cartridge 120, causes movement ofthe mixing elements within the cartridge 120 to encourage the reagentbeads to dissolve in the blood contained within the mixing chambers 134a-e.

In step 650, thromboelastometry testing is started. For example, theanalyzer console can begin to analyze the data produced thethromboelastometry assemblies in regard to the reciprocating rotation ofthe shafts that are coupled with the pins 138 a-e located in the cups136 a-e of the cartridge (refer to FIGS. 8A-8H). In someimplementations, the analyzer console may begin to analyze the dataproduced by some of the thromboelastometry assemblies prior to beginningto analyze the data produced by others of the thromboelastometryassemblies. For example, as described above in reference to FIGS. 8A-8H,the analyzer console may begin to first analyze the data produced by thethromboelastometry assembly pertaining to cup 136 e. Subsequently, theanalyzer console may begin to analyze the data produced by thethromboelastometry assembly pertaining to cup 136 d, and so on.

In step 660, the analyzer console displays the results of thethromboelastometry. Such results may be displayed concurrently with theperformance of the testing and at the completion of the testing. Theresults can be displayed via the user interface of the analyzer console,such as on the touchscreen display. The results can be displayed usingqualitative graphical representations and quantitative parameters.

In step 670, the analyzer console can unclamp the cartridge at thecessation of the testing. In some cases, such cessation may be initiatedby a user input to the analyzer console to stop the testing, or by thecompletion of the test assays, or by the expiration of a time-basedparameter. The unclamping may be performed, for example, by thehorizontal translation of the moveable block sub-assembly. After theunclamping, the cartridge can be removed from the analyzer console.

A number of embodiments of the invention have been described.Nevertheless, it will be understood that various modifications may bemade without departing from the spirit and scope of the invention.Accordingly, other embodiments are within the scope of the followingclaims.

What is claimed is:
 1. A measuring system for measuring viscoelasticcharacteristics of a sample liquid, comprising: at least one interfaceelement; at least one shaft rotatably supported by the interface elementto be rotated by drive means; a cartridge device fixed to the interfaceelement for holding the sample liquid, the cartridge device having aprobe element, the probe element of the cartridge device cooperatingwith the at least one shaft; at least one detector cooperating with theshaft for measuring viscoelastic characteristics of a portion of thesample liquid in contact with the probe element; and a controller tocontrol the measuring system.
 2. The measuring system of claim 1,wherein the cartridge device comprises: a cartridge body having: atleast one testing chamber formed therein, the at least one testingchamber configured for receiving a portion of a sample liquid, and acircumferential wall, the circumferential wall comprising a sample inputport defined in the circumferential wall of the at least one testingchamber.
 3. The measuring system of claim 2, wherein the probe elementis movable within the at least one testing chamber of the cartridgedevice for measuring viscoelastic characteristics of the sample liquid.4. The measuring system of claim 2, wherein the cartridge device furthercomprises: a first cover attached at a first side of the cartridgedevice, the first cover comprising a first tab and a second tab; asecond cover attached at a second side of the cartridge device, oppositeto the first side, the second cover comprising a third and fourth tab.5. The measuring system of claim 4, wherein the first, second, third,and fourth tabs prevent the probe element from being removed from the atleast one testing chamber, while allowing the probe element to movevertically by at least one millimeter.
 6. The measuring system of claim4, wherein the probe element comprises: a shoulder at a distal end ofthe probe element, a ring at a proximal end of the probe element,wherein an opening between the first, second, third, and fourth tabs aresmaller than an outer diameter of the ring, wherein the first, second,third, and fourth tabs are configured to retain the probe element insideof the test chamber, and a cylindrical body between the shoulder and thering, wherein an outer diameter of the shoulder and the ring is largerthan an outer diameter of the cylindrical body.
 7. The measuring systemof claim 6, wherein the shoulder of the probe element is positionedbelow the sample input port.
 8. The measuring system of claim 1, whereinthe sample liquid is a blood sample.
 9. The measuring system of claim 1,wherein the cartridge device has a plurality of testing chambers, eachhaving a respective probe element arranged therein.
 10. The measuringsystem of claim 1, wherein the cartridge device comprises: at least onemixing chamber fluidly coupled to a testing chamber, the mixing chamberhaving an outlet port; a valve between the outlet port of the mixingchamber and an inlet port of the testing chamber, the valve configuredto prevent flow of the sample liquid from the mixing chamber into thetesting chamber; and a pressure application port fluidly coupled to themixing chamber, the pressure application port for applying a source ofair pressure into the mixing chamber to allow the sample liquid to flowfrom the mixing chamber into the testing chamber.
 11. The measuringsystem of claim 10, wherein the at least one mixing chamber comprisingan array of posts restricting movement of a set of reagent beads withinthe mixing chamber, individually separating each of the set of reagentsbeads from other reagent beads of the set of reagent beads, andseparating the set of reagents beads from a mixing element retainedwithin the mixing chamber.
 12. The measuring system of claim 1, whereinthe probe element comprises a lower portion configured to engage withthe sample liquid.
 13. The measuring system of claim 1, wherein theprobe element is configured to prevent semi-coagulated sample liquidfrom escaping a testing chamber.
 14. A method for measuring viscoelasticcharacteristics of a sample liquid by means of a measuring system ofclaim 1, comprising: providing the cartridge device having at least onetesting chamber with the probe element arranged therein; attaching thecartridge device to the interface element, the shaft being inserted intothe probe element; filling the testing chamber of the cartridge devicewith the sample liquid; rotating the shaft in an oscillating motionaround a rotation axis; and measuring viscoelastic characteristics ofthe sample liquid by detecting the rotation of the shaft.
 15. Acartridge device for use with a blood coagulation measuring system,comprising: a plurality of blood testing chambers for receiving aportion of a blood sample to measure blood coagulation characteristics;a movable pin element positioned in each of the blood testing chambers;and a sample input port defined in a circumferential wall of each of theblood testing chambers, wherein the sample input port and the outerdiameter of the movable pin element are at least a minimum clearancedistance apart, and wherein the minimum clearance distance preventsstable bridging of the blood sample between the sample input port andthe movable pin element.
 16. The cartridge device of claim 15, whereinthe minimum clearance distance is 1.5 mm.
 17. The cartridge device ofclaim 15, wherein each movable pin element comprises a lower portionconfigured to engage with the blood sample in its corresponding bloodtesting chamber.
 18. The cartridge device of claim 15, wherein thesample input port of each of the blood testing chambers is connected tocorresponding ductwork fluidically linked to a mixing chamber.
 19. Thecartridge device of claim 15, further comprising a plurality of mixingchambers each corresponding to one of the blood testing chambers, eachmixing chamber comprising a reagent configured to be mixed with theblood sample before the blood sample is transported via a ductwork tothe sample input port and into the corresponding blood testing chamber.20. The cartridge device of claim 19, wherein each of the mixingchambers comprises a different reagent so that each of the blood testingchambers receives a corresponding portion of the blood sample mixed withthe different reagent.